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Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

Background: Chemotherapy, together with immune checkpoint inhibitors, improves outcomes vs chemotherapy alone for patients (pts) with metastatic (m)TNBC PD-L1+ disease. Most of these pts progress within a year. In a previous study, D (anti-PD-L1) combined with chemotherapy enhanced antitumor immune responses in early TNBC (Loibl. Ann Oncol 2019). In TNBC, activation of the PI3K/AKT/PTEN pathway and high CD73 expression are common. BEGONIA is an ongoing 2-part, multicenter, multi-arm, open-label platform study, evaluating safety and efficacy of D or D+P combined with novel therapies as first-line treatment for mTNBC (NCT03742102). Preliminary results from 2 arms were presented at ASCO 2021 (Abstract #1023). Here, we report results from Arm 1 D+P, Arm 2 D+P+C, and Arm 5 D+P+O. C is an oral, selective, ATP-competitive catalytic inhibitor of all 3 AKT isoforms, and O is a mAb targeting CD73. Methods: Eligible pts had untreated, unresectable, locally advanced or metastatic TNBC. In Arms 1 and 5, pts received D 1500 mg IV Q4W + P 90 mg/m2 IV day (d)1, d8, d15 of every cycle. Pts in Arm 5 also received O 3000 mg IV on d1 and d15 for the first 2 cycles, then Q4W. In Arm 2, pts received D 1500 mg IV Q4W + P 80/90 mg/m2 IV in 4-week cycles (d1, d8, d15, 1 week off) + C 400 mg BID in 4-week cycles (d2-5 × 3 weeks, 1 week off). Primary objectives were safety and tolerability. Secondary endpoints included objective response rate (ORR) and duration of response. Tumors were assessed Q8W per RECIST v1.1. The first 6 pts treated in Arms 2 and 5 were evaluated for dose-limiting toxicities (DLTs), with additional pts enrolled if treatment was tolerated. PD-L1 expression was assessed retrospectively. Previously presented data from Arm 1 D+P, are included for reference (Schmid. ASCO 2021, #1023). Results: In Arm 2 (data cutoff Mar 2021), 30 pts received D+P+C (15 P[80], 15 P[90]; total 13 ongoing); 2 pts (6.7%) discontinued all treatment due to AEs. The rates of dose delays were 13 pts (43%) for D and 15 (50%) for P; dose interruptions were 1 (3%) for D, 12 (40%) for P, 15 (50%) for C; dose reductions were 12 (40%) for P and 14 (47%) for C. Treatment-related (tr)SAEs and G3/4 trAEs were experienced by 7 (23%) and 22 (73%) pts. In Arm 5 (data cutoff Sep 2020), 33 pts received D+P+O (14 ongoing); no pts discontinued due to AEs. The rates of dose delays were 13 pts (39%) for D, 10 (30%) for P, 10 (30%) for O; dose interruptions were 2 (6%) for D, 10 (30%) for P, 3 (9%) for O; and dose reductions were 12 (36%) for P. trSAEs and G3/4 trAEs were experienced by 1 (3%) and 5 (15%) pts. In both arms, there were no DLTs or deaths due to AEs. The Table presents follow-up time and efficacy outcomes for Arms 1, 2, and 5. Responses were observed regardless of PD-L1 expression. The potential value of mutations in the PI3K pathway and CD73 expression as predictive biomarkers will be discussed for Arms 2 and 5, respectively. Updated data for Arm 1 will be presented. Conclusions: The safety profiles of triplet combinations in Arms 2 and 5 were consistent with the individual agents; however, in Arm 2, there was a relatively high rate of G3/4 trAEs but a low discontinuation rate for AEs. Although BEGONIA was not designed to compare activity across arms and numbers were small, the ORR of each triplet therapy was numerically similar to D+P. Biomarker analysis may elucidate pts that benefit from the combination of C or O with D+P. Funding: AstraZeneca Table. Efficacy outcomes in Arms 1, 2, and 5 of BEGONIAArm 1Arm 2Arm 5D+P N=23D+P(80)+C n=15D+P(90)+C n=15All D+P+C N=30D+P+O N=33Duration of follow-up at data cutoff, months, median (range)16.6 (8.5-19.8)6.7 (2-9)16.8 (6-21)8.2 (2-21)8.6 (4.1-14.6)Confirmed ORR, n (%)13 (56.5)8 (53.3)8 (53.3)16 (53.3)15 (45.5)95% CI34.5-76.826.6-78.726.6-78.7NC28.1-63.3CR, n10111PR12871514SD (Unconfirmed PR)7 (3)6 (2)4 (2)10 (4)13 (4)PD31345Percentage with ongoing response at data cutoff53.8%75.0%25.0%50.0%66.7%Arm 1 data cutoff was Sep 2020. C, capivasertib; CI, confidence interval; CR, complete response; D, durvalumab; NC, not calculable; O, oleclumab; ORR, objective response rate; P, paclitaxel; PD, progressive disease; PR, partial response; SD, stable disease. Citation Format: Peter Schmid, Zbigniew Nowecki, Seock-Ah Im, Wei-Pang Chung, Simon Lord, Anne Armstrong, Cynthia X Ma, Robert Huisden, Ross Stewart, Rakesh Kumar, Gaia Schiavon, Hannah Dry, Ana Nunes, Kyung Hae Jung, Yeon Hee Park. BEGONIA: Phase 1b/2 study of durvalumab (D) combinations in locally advanced/metastatic triple-negative breast cancer (TNBC): Results from Arm 1 D + paclitaxel (P), Arm 2 D+P + capivasertib (C), and Arm 5 D+P + oleclumab (O) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD10-03.

Background: Male breast cancer is a rare disease accounting for less than 1% of all breast cancer diagnoses worldwide. Male breast cancer is not very well understood. Prospective data in the management of male breast cancer are lacking and majority of treatment strategies are adopted from the established guidelines for breast cancer in women. The understanding of biology, clinical presentation, genetics, and management of MBC is evolving but there still remains a large knowledge gap due to the rarity of this disease.Patients and methods: The aim of this retrospective study is to analyze the epidemiologic, clinical and therapeutic problems with this disease and to compare some cancer aspects between male and female in 67 cases collected at Maria Sklodowska Curie National Research Institute of Oncology in Warsaw between 05.2011 and 02.2021. Patients with a primary diagnosis of breast cancer were identified in the our database.Results: The median age was 65 years (range 22-93 years). Family history was present in 15 (22%) men and in as 17 pts (25%) other cancer were diagnosed (prostate cancer, melanoma, Hodgkin lymphoma, NET, thyroid cancer). Early, locally advanced, and metastatic disease were seen in 44 (65%), 9 (14%), and 14 (21%) men, respectively. Majority (59, 88%) of men had invasive ductal carcinoma histology. In radically treated 44 men, neoadjuvant chemotherapy was given to 20 (29%) patients with pCR in 1 (1.5%) and neoadjuvant hormonotherapy (tamoxifen) in 5 (7.5%) of pts. Estrogen receptor, PR, and human epidermal growth factor receptor 2/neu positive were seen in 62 (92.5%), 60 (89.5%), and 15 (22%) patients, respectively. Triple negative breast cancer were diagnosed in 4 (6%) pts. During the follow-up period locoregional recurrence occurred in 1 (1.5%) and distant metastasis in 15 (22%) men, respectively. Bone was the most representative site of metastases (20, 69%). In contrast to women with breast cancer, who have mainly osteolytic metastases (75-80%), our analysis found that men were predominantly osteoblastic lesions (10, 50% pts with bone mts). There was 31 cases of death (46%). Death was usually due breast cancer progression (29, 43%).Conclusion: This analysis found that men with breast cancer had a higher risk of second primaries cancer. Bone was the most representative site of metastases, but they are mainly osteoblastic lesions. Citation Format: Agnieszka Irena Jagiello-Gruszfeld, Pawel Winter, Rafal Wojcik, Michal Kunkiel, Renata Sienkiewicz, Roman Dubianski, Anna Majstrak-Hulewska, Zbigniew Nowecki. Male breast cancer in a retrospective study from the Maria Sklodowska Curie National Research Institute of Oncology in Warsaw, Poland [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-23-03.

PURPOSE Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor–positive breast cancer has not been confirmed. PATIENTS AND METHODS In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer–free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival. RESULTS Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial. CONCLUSION At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor–positive breast cancer.

PURPOSE We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)–positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1). METHODS The phase III KAITLIN study ( NCT01966471 ) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor–negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing. RESULTS The median follow-up was 57.1 months (interquartile range, 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range, 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade ≥ 3 (55.4% v 51.8%) and serious adverse events (23.3% v 21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80). CONCLUSION The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC.

Purpose PI3K/AKT pathway alterations are frequent in hormone receptor-positive (HR+) breast cancers. IPATunity130 Cohort B investigated ipatasertib–paclitaxel in PI3K pathway-mutant HR+ unresectable locally advanced/metastatic breast cancer (aBC). Methods Cohort B of the randomized, double-blind, placebo-controlled, phase 3 IPATunity130 trial enrolled patients with HR+ HER2-negative PIK3CA/AKT1/PTEN-altered measurable aBC who were considered inappropriate for endocrine-based therapy (demonstrated insensitivity to endocrine therapy or visceral crisis) and were candidates for taxane monotherapy. Patients with prior chemotherapy for aBC or relapse 2, days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Results Overall, 146 patients were randomized to ipatasertib–paclitaxel and 76 to placebo–paclitaxel. In both arms, median investigator-assessed PFS was 9.3 months (hazard ratio, 1.00, 95% CI 0.71–1.40) and the objective response rate was 47%. Median paclitaxel duration was 6.9 versus 8.8 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively; median ipatasertib/placebo duration was 8.0 versus 9.1 months, respectively. The most common grade ≥ 3 adverse events were diarrhea (12% with ipatasertib–paclitaxel vs 1% with placebo–paclitaxel), neutrophil count decreased (9% vs 7%), neutropenia (8% vs 9%), peripheral neuropathy (7% vs 3%), peripheral sensory neuropathy (3% vs 5%) and hypertension (1% vs 5%). Conclusion Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered HR+ HER2-negative aBC. The ipatasertib–paclitaxel safety profile was consistent with each agent’s known adverse effects. Trial registration NCT03337724.

BackgroundPoly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer.MethodsWe conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival.ResultsA total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P

Neoadjuvant therapy (NAT) is increasingly applied in patients with initially inoperable breast cancers and, frequently, in those with tumours that are initially operable, too. In most cases, the response to the applied NAT affects the scope of surgical treatment and radiotherapy, and in some situations also the complementary systemic postoperative treatment. The available studies indicate importance of response to NAT within the breast and regional lymph nodes. Assessment of response to treatment allows personalization of treatment and in some cases a change of therapy, which improves long-term outcomes. This article summarizes the current rules of conduct in patients with early breast cancer qualified for neoadjuvant thera­py, paying attention to the practical aspects and possibilities of national health insurance-covered therapies in Poland. It discusses in detail the applied regimens of systemic therapy, surgical techniques, eligibility rules and complementary radiotherapy. Systems for assessing response to neoadjuvant treatment are also presented.

Purpose Intravenous trastuzumab, pertuzumab, and docetaxel are first-line standard of care for patients with HER2-positive metastatic breast cancer (mBC). MetaPHER is the first study assessing the safety and tolerability of subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy in a global patient population with HER2-positive mBC. Methods In this open-label, single-arm, multicenter, phase 3b study, eligible patients were ≥ 18 years old with histologically/cytologically confirmed previously untreated HER2-positive mBC. All received ≥ 1 subcutaneous trastuzumab 600 mg fixed dose plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance: 420 mg/kg) and docetaxel (≥ 6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy. Results At clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia; the most common grade ≥ 3 events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%. Conclusions Safety and efficacy with subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in mBC are consistent with historical evidence of intravenous trastuzumab with this combination. Findings further support subcutaneous administration not affecting safety/efficacy profiles of trastuzumab in HER2-positive BC with increased flexibility in patient care. A fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection has recently been approved for the treatment of HER2-positive early/mBC, further addressing the increasing relevance of and need for patient-centric treatment strategies. Trial registration NCT02402712

Background Camizestrant (C), a next-generation oral selective estrogen receptor (ER) antagonist and degrader (ngSERD) has shown promising clinical activity in ER+ breast cancer (BC) in the Phase 1 SERENA-1 study1,2 with a dose-dependent safety profile. The Phase 2 randomized SERENA-2 study (NCT04214288) initially assessed three doses of C vs fulvestrant (F) in post-menopausal women with ER+ HER2˗ BC with disease recurrence or progression after ≤1 endocrine therapy (ET) in the advanced setting. Methods SERENA-2 evaluated efficacy and safety of C 75, 150 or 300 mg monotherapy QD vs F (per label). Eligible patients were randomized 1:1:1:1. The Primary objective was to determine clinical efficacy of C vs F by investigator-assessed progression-free survival (PFS). Secondary endpoints included objective response rate, response duration, clinical benefit rate at 24 weeks, overall survival and safety. Patients had no prior F or oral SERD and ≤1 ET and ≤1 chemotherapy (CTX) in the advanced setting. To assess the impact of prior CDK4/6 inhibitor (CDK4/6i) treatment, randomization was stratified so that 50% of patients had prior CDK4/6i. Planned enrolment of 288 patients began in April 2020. The C 300 arm was closed after 20 patients were enrolled, changing target enrolment to 236. By August 2021, 240 patients had been randomized. Primary analysis was triggered when 108 progression events (75% maturity) had occurred in the best performing pair (C vs F) in August 2022. Efficacy analyses compared C 75 and 150 mg doses with F, with no formal analyses of C 300 vs F. 108 events for pairwise comparison vs F gave 86% power at the 2-sided 10% significance level. Primary analyses used a Cox proportional hazards model to compare PFS, adjusting for prior CDK4/6i and lung/liver metastases. ESR1 mutations (ESR1m) were detected in plasma samples using next-generation sequencing. Results 119/240 (49.6%) patients had had prior CDK4/6i therapy. At baseline, 88 (36.7%) patients had detectable ESR1m and 140 (58.3%) had lung/liver metastases. Prior CTX or ET rates in the advanced setting were 19.2 and 65.4%. Treatment-emergent adverse events (AEs) (grade ≥3) occurred in 77.0 (12.2), 90.4 (21.9) and 68.5 (13.7) % of patients in the C 75, C 150 and F arms. AEs leading to treatment discontinuation occurred in 2.7, 0 and 0% of patients in the C 75, C 150 and F arms. The most common AEs considered by the investigator to be causally related to study drug were photopsia (18.4%) and (sinus) bradycardia (13.6%) – all were grade 1 or 2. Hot flush (2.7%) and myalgia (2.7%) were the most common AEs related to F. Conclusions SERENA-2 is the first Phase 2 trial investigating multiple dose levels of an ngSERD vs F in post-menopausal women with advanced ER+ HER2˗ BC with disease recurrence or progression after ≤1 ET in the advanced setting. C at both 75 and 150 mg dose levels showed a statistically significant and clinically meaningful benefit in PFS vs F in the overall study population, and was well tolerated. The results of SERENA-2 support the further development of C in ER+ HER2- BC. Acknowledgements AstraZeneca sponsored this trial and funded medical writing support from Helen Heffron (InterComm International). References 1. Baird R, Oliveira M, Ciruelos Gil EM, et al. SABCS 2020 Virtual Meeting. Abstract PS11-05; 2. Oliveira M, Hamilton EP, Incorvati J et al. ASCO 2022 Annual Meeting, Chicago, IL, USA. Abstract 1032. Citation Format: Mafalda Oliveira, Denys Pominchuck, Zbigniew Nowecki, Erika Hamilton, Yaroslav Kulyaba, Timur Andabekov, Yevhen Hotko, Tamar Melkadze, Gia Nemsadze, Patrick Neven, Yuriy Semegen, Vladmir Vladmirov, Claudio Zamagni, Hannelore Denys, Frederic Forget, Zsolt Horvath, Alfiya Nesterova, Maxine Bennett, Bistra Kirova, Teresa Klinowska, Justin Lindemann, Delphine Lissa, Alastair Mathewson, Christopher Morrow, Zuzana Traugottova, Ruaan Van Zyl, Ekaterine Arkania. GS3-02 Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose Phase 2 SERENA-2 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS3-02.

Neoadjuvant therapy (NAT) is increasingly applied in patients with initially inoperable breast cancers and, frequently, in those with tumours that are initially operable, too. In most cases, the response to the applied NAT affects the scope of surgical treatment and radiotherapy, and in some situations also the complementary systemic postoperative treatment. The available studies indicate importance of response to NAT within the breast and regional lymph nodes. Assessment of response to treatment allows personalization of treatment and in some cases a change of therapy, which improves long-term outcomes. This article summarizes the current rules of conduct in patients with early breast cancer qualified for neoadjuvant thera­py, paying attention to the practical aspects and possibilities of national health insurance-covered therapies in Poland. It discusses in detail the applied regimens of systemic therapy, surgical techniques, eligibility rules and complementary radiotherapy. Systems for assessing response to neoadjuvant treatment are also presented.

Summary Background Palbociclib added to endocrine therapy improves progression-free survival in hormone-receptor-positive, HER2-negative, metastatic breast cancer. The PALLAS trial aimed to investigate whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine therapy alone in patients with hormone-receptor-positive, HER2-negative, early-stage breast cancer. Methods PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study that enrolled patients at 406 cancer centres in 21 countries worldwide with stage II–III histologically confirmed hormone-receptor-positive, HER2-negative breast cancer, within 12 months of initial diagnosis. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients were randomly assigned (1:1) in permuted blocks of random size (4 or 6), stratified by anatomic stage, previous chemotherapy, age, and geographical region, by use of central telephone-based and web-based interactive response technology, to receive either 2 years of palbociclib (125 mg orally once daily on days 1–21 of a 28-day cycle) with ongoing standard provider or patient-choice adjuvant endocrine therapy (tamoxifen or aromatase inhibitor, with or without concurrent luteinising hormone-releasing hormone agonist), or endocrine therapy alone, without masking. The primary endpoint of the study was invasive disease-free survival in the intention-to-treat population. Safety was assessed in all randomly assigned patients who started palbociclib or endocrine therapy. This report presents results from the second pre-planned interim analysis triggered on Jan 9, 2020, when 67% of the total number of expected invasive disease-free survival events had been observed. The trial is registered with ClinicalTrials.gov (NCT02513394) and EudraCT (2014-005181-30). Findings Between Sept 1, 2015, and Nov 30, 2018, 5760 patients were randomly assigned to receive palbociclib plus endocrine therapy (n=2883) or endocrine therapy alone (n=2877). At the time of the planned second interim analysis, at a median follow-up of 23·7 months (IQR 16·9–29·2), 170 of 2883 patients assigned to palbociclib plus endocrine therapy and 181 of 2877 assigned to endocrine therapy alone had invasive disease-free survival events. 3-year invasive disease-free survival was 88·2% (95% CI 85·2–90·6) for palbociclib plus endocrine therapy and 88·5% (85·8–90·7) for endocrine therapy alone (hazard ratio 0·93 [95% CI 0·76–1·15]; log-rank p=0·51). As the test statistic comparing invasive disease-free survival between groups crossed the prespecified futility boundary, the independent data monitoring committee recommended discontinuation of palbociclib in patients still receiving palbociclib and endocrine therapy. The most common grade 3–4 adverse events were neutropenia (1742 [61·3%] of 2840 patients on palbociclib and endocrine therapy vs 11 [0·3%] of 2903 on endocrine therapy alone), leucopenia (857 [30·2%] vs three [0·1%]), and fatigue (60 [2·1%] vs ten [0·3%]). Serious adverse events occurred in 351 (12·4%) of 2840 patients on palbociclib plus endocrine therapy versus 220 (7·6%) of 2903 patients on endocrine therapy alone. There were no treatment-related deaths. Interpretation At the planned second interim analysis, addition of 2 years of adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting. Long-term follow-up of the PALLAS population and correlative studies are ongoing. Funding Pfizer.

Background: Intravenous pertuzumab (P IV) + trastuzumab (H IV) + chemotherapy (CT) improves outcomes in patients (pts) with HER2-positive breast cancer, compared with H + CT.A new subcutaneous (SC) formulation, for the first time combining two monoclonal antibodies, P + H, with recombinant human hyaluronidase in one vial, was developed. This ready-to-use fixed-dose combination (PH FDC) is administered subcutaneously into the thigh over 5-8 minutes. The dose of H SC was confirmed in the phase III HannaH trial (NCT00950300) and the dose of P SC was established in a phase Ib study (NCT02738970). We report the first results from FeDeriCa (NCT03493854), which was designed to assess the pharmacokinetics, efficacy, and safety of this novel SC PH FDC compared with H IV + P IV in pts with HER2-positive early breast cancer in the neoadjuvant-adjuvant setting. Methods: Pts with centrally confirmed HER2-positive invasive breast cancer (tumor >2 cm, or node-positive disease; Stage II-IIIC) were randomized 1:1 to receive 8 cycles of CT in the neoadjuvant setting with H IV (loading dose 8 mg/kg, maintenance 6 mg/kg) + P IV (loading dose 840 mg, maintenance 420 mg) (Arm A) or CT per Arm A + PH FDC (loading dose 1200 mg P SC/600 mg H SC, maintenance 600 mg each; Arm B) administered q3w during cycles 5-8. CT was investigator’s choice of either 4 cycles of dose-dense doxorubicin + cyclophosphamide q2w → 4 cycles of weekly paclitaxel (total: 12 weeks), or 4 cycles of doxorubicin + cyclophosphamide q3w → 4 cycles of docetaxel q3w. Post-surgery, pts continued anti-HER2 treatment per randomization to complete 18 cycles. The primary objective was noninferiority (NI) of the pre-dose cycle 8 P serum trough concentration (Ctrough) within the PH FDC versus P IV (NI margin for the lower bound of the 90% confidence interval [CI] of the geometric mean ratio [GMR]: ≥0.8). Key secondary objectives were NI of pre-dose cycle 8 H Ctrough within the PH FDC versus H IV, total pathologic complete response in the breast and axilla (ypT0/is, ypN0; tpCR), and safety (primary cardiac events were defined as heart failure [New York Heart Association III + IV] with significant left ventricular ejection fraction [LVEF] decline; cardiac death. Secondary cardiac events were defined as LVEF decline ≥10% from baseline to below 50% and confirmed LVEF decline). Results: Five-hundred pts were randomized (252 to Arm A, 248 to Arm B - ITT and safety populations) from 06/14/18-12/24/18 at 122 sites. At clinical cutoff (07/04/19), 242 pts (96.0%) in Arm A and 234 (94.4%) in Arm B completed the neoadjuvant treatment phase. Baseline pt demographics and disease characteristics were well balanced between arms.The study met its primary endpoint: P GMR was 1.22 (90% CI 1.14-1.31) with the lower limit of the 90% CI being above the prespecified NI margin of 0.8. H GMR was 1.33 (90% CI 1.24-1.43), meeting the NI criteria. tpCR rates were comparable between arms (59.5%; 95% CI 53.2-65.6 in Arm A and 59.7%; 95% CI 53.3-65.8 in Arm B) and were similar to other P + H + CT trials. Overall safety, including cardiac safety, was comparable between arms (Table). Safety was as expected for P + H + CT trials. Conclusions: SC PH FDC demonstrated noninferior pre-dose cycle 8 P + H Ctrough to that of P IV + H IV, with comparable efficacy and safety. PH FDC offers a faster and simpler method of P + H administration for HER2-positive breast cancer. Pts, %Arm A n = 252Arm B n = 248Any AE in >50% of pts99.6100Alopecia70.277.0Nausea60.358.9Diarrhea55.258.5Grade ≥352.848.8Serious17.916.1CardiacPrimary00.8Secondary3.61.6Asymptomatic LVEF decline needing treatment/discontinuation4.02.0Death0.4*0.4** Unrelated to HER2 treatment Citation Format: Antoinette R Tan, Seock-Ah Im, Andre Mattar, Ramon Colomer, Daniil Stroyakovskii, Zbigniew Nowecki, Michelino De Laurentiis, Jean-Yves Pierga, Kyung Hae Jung, Christian Schem, Sarah Heeson, Mahesh Shivhare, Whitney P. Kirschbrown, Eleonora Restuccia, Tanja Badovinac Crnjevic, Christian Jackisch. Subcutaneous administration of the fixed-dose combination of trastuzumab and pertuzumab in combination with chemotherapy in HER2-positive early breast cancer: Primary analysis of the phase III, multicenter, randomized, open-label, two-arm FeDeriCa study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD4-07.

Background Previous trials showed that fixed-dose subcutaneous trastuzumab and hyaluronidase-oysk (Herceptin Hylecta™; H SC) was non-inferior to weight-based intravenous trastuzumab (Herceptin®; H IV) in terms of pathologic complete response and serum trough concentration in HER2-positive early breast cancer (BC), with a comparable safety profile (NCT00950300), and demonstrated a compelling patient (pt) preference for H SC (NCT01401166). IV pertuzumab (PERJETA®; P IV) + H IV + docetaxel (D IV) was also shown to significantly improve progression-free survival (PFS) and overall survival vs. placebo + H IV + D IV in HER2-positive metastatic BC (NCT00567190). Here we report results from the final analysis of MetaPHER (NCT02402712), the largest study to evaluate safety and tolerability of first-line H SC + P IV + D IV for HER2-positive metastatic/locally advanced BC. Earlier analyses have been reported (Kümmel SABCS 2016; P4-21-42; Kümmel ESMO 2018; 323P). Methods Pts were ≥18-year-old females who had received no previous systemic non-hormonal anticancer therapy for their disease, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and a left ventricular ejection fraction (LVEF) ≥50%. Brain metastases and concomitant hormone therapy were allowed. Pts received 600 mg H SC + 840 mg loading/420 mg maintenance doses of P IV + ≥6 cycles of D IV (75 mg/m2→100 mg/m2; >6 cycles were given at the investigator’s discretion) every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end. The primary objective was to evaluate safety and tolerability. Adverse events (AEs) were graded per National Cancer Institute - Common Terminology Criteria for Adverse Events version 4.0; left ventricular systolic dysfunction (LVSD) was classified according to the New York Heart Association Functional Classification system. Safety results are descriptive. Exploratory efficacy endpoints were PFS and objective response rate (ORR). Results Four hundred eighteen pts were enrolled; 412 were treated and analyzed for safety, and 160 remained on treatment at study end. Data cutoff was May 23, 2019 with median follow-up of 27 months (max. 45 months). Baseline demographics were similar to the interim analysis. Median cycles of H SC, P IV, and D IV were 22.0, 21.5, and 6.0, respectively (some discontinued P IV due to toxicity but remained on H SC per the protocol). Most pts experienced ≥1 any-grade AE (406; 98.5%); 221 (53.6%), grade ≥3 AEs; 107 (26.0%), serious AEs; 87 (21.1%), AEs leading to withdrawal from any study treatment; 87 (21.1%), investigator-reported administration-related and local injection-site reactions (21 [5.1%] H SC-related). There were 87 deaths (21.1% of pts): 73 (17.7%) from disease progression, nine (2.2%) due to AEs, and five (1.2%) due to other causes after treatment discontinuation. Three pts (0.7%) experienced grade ≥3 cardiac AEs, and one (0.2%) a serious AE suggestive of congestive heart failure. Of the 396 pts with LVEF measurements at baseline and ≥1 post-baseline visit, 40 (10.1%) had LVEF drops (to Citation Format: Sherko Kümmel, Carlo A Tondini, Jacinta Abraham, Zbigniew Nowecki, Bartosz Itrych, Erika Hitre, Bogusława Karaszewska, Alejandro Juarez, Flavia Morales-Vásquez, Jose Manuel Pérez García, Servando Cardona-Huerta, Mark Benyunes, Eleonora Restuccia, Adam Knott, Estefanía Monturus, Marco Sequi, Miguel Martín. Subcutaneous trastuzumab and hyaluronidase-oysk with intravenous pertuzumab and docetaxel in HER2-positive advanced breast cancer: Final analysis of the phase IIIb, multicenter, open-label, single-arm MetaPHER study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-05.

Further personalization is needed to improve the outcomes of breast cancer treatment. It is necessary to find new inexpensive and easily evaluated predictive markers. In this study, we determined serum level of Aurora A (AURKA), thymidine kinase 1 (TK1) and human epidermal growth factor receptor type 3 (HER3) by enzyme immunoassay ELISA. We collected peripheral blood sera of 119 women with breast cancer before neoadjuvant treatment and the control group of 47 randomly selected healthy women. After treatment we analyzed clinical data: age, initial TNM stage, tumor receptors expression: estrogen (ER), progesterone (PGR), epidermal growth factor receptor type 2 (HER2), Ki67, histological malignancy grade, biological subtype, and response to neoadjuvant treatment in residual cancer burden (RCB) classification. Pathologic complete response (PCR) was achieved in 41 patients (34.45%). In univariate analysis patients with higher AURKA levels were more likely to obtain PCR (p=0.039). In multivariate analysis we used the logit regression model with PCR as the dependent. The effect of AURKA concentration ≥4.75 ng / mL on the chance of achieving PCR was found (OR: 3.5; 95%CI: 1.2-10.1; p = 0.023). Other significant PCR factors included: node status (OR: 0.503; 95% CI: 0.263-0.965; p = 0.039), negative PGR expression (OR: 0.104; 95% CI: 0.038-0.284; p < 0.001), and Ki67 >20% (OR: 5.44; 95% CI: 1.24-23,9; p < 0.025). There was no significance in marker concentrations and clinical features nor between breast cancer patients and control group. The outcomes suggest that serum AURKA level is a potential PCR prediction marker in neoadjuvant breast cancer treatment. Further studies are needed to confirm our observations.

Background Margetuximab (M) is an investigational Fc-engineered anti-HER2 monoclonal antibody that targets the same epitope as trastuzumab (T). Compared with T, M has higher affinity for both the 158V (high-binding) and 158F (low-binding) allotypes of the activating Fc receptor CD16A. M enhances innate immunity more effectively than T in vitro, including CD16A-mediated antibody-dependent cellular cytotoxicity. Samples collected from patients (pts) before and after single-agent treatment also demonstrate that M induces HER2-specific adaptive immune responses, including both T- and B-cell responses. The SOPHIA trial (NCT02492711) in pts with pretreated HER2+ MBC showed that M+chemotherapy (chemo) improved progression-free survival vs T+chemo, with comparable safety. A pooled analysis of M safety across 3 clinical trials is presented. Methods Study 01 (NCT01148849), an ongoing Phase 1 dose-finding/safety study of M monotherapy, enrolled 66 pts with advanced HER2+ carcinomas, including 27 with MBC. Study 02 (NCT01828021), a completed Phase 2 study of M monotherapy in low-expressing HER2+ MBC, enrolled 25 pts. Study 04 (NCT02492711), an ongoing Phase 3 study in pts with pretreated HER2+ MBC to compare M + chemo vs T + chemo, randomized 536 pts, of whom 264 and 265 received M and T, respectively. The pooled safety population includes all pts who received any M in Study 01 (cutoff 01Oct2015), Study 02 (cutoff 02Aug2017), and Study 04 (cutoff 10OCT2018). Treatment-emergent adverse events (AEs), defined as AEs that began or worsened in severity on or after first dose of study drug through an End of Treatment Visit or 28 days after last study treatment, are reported. Results Of 355 pts that received at least 1 dose of M, 295 received 15 mg/kg Q3W, and 60 received other doses from 0.1 - 18 mg/kg. Median (mean, range) number of cycles for all dose levels was 5.0 (6.6, 1-43), higher on Study 04 (6.0) than Study 01 (1-3 across dose groups) or Study 02 (2.0). Most pts (347 [97.7%]) experienced at least 1 AE, and about half (173 [48.7%]) had at least 1 Grade >/= 3 AE. Serious AE (SAE) incidence across studies was low (58 [16.3%]), and 21 pts (5.9%) discontinued M due to AEs. Most frequently reported AEs (>/= 20%) were fatigue (124 [34.9]), nausea (103 [29.0%]), diarrhea (75 [21.1%]), and neutropenia (75 [21.1%]). Blood/lymphatic system disorders were the most frequent events by SOC, and largely restricted to Study 04. Increased neutropenia on M (26.1%), relative to T (20.4%), was observed in Study 04 yet both febrile neutropenia (M 3.0%, T 4.5%) and infections (M 36.4%, T 39.6%) were higher on T. By contrast, Study 01 and Study 02 revealed no tendency of M monotherapy to cause neutropenia. Overall, infusion related reactions (IRRs) were observed in 51 pts (14.4%), primarly at first infusion, including serious IRRs in 5 (1.4%). Also, 34 pts (9.6%) had > 15% reduction in LVEF with a median time to > 15% reduction of 49 days. In all pts with complete follow-up, these LVEF reductions were asymptomatic and reversible. No M-induced cardiac conduction abnormalities were noted. In Study 04, similar proportions in both groups experienced AEs (M 97.7%, T 96.2%), including Grade >/= 3 AEs (M 52.3%, T 48.3%), SAEs (M 14.8%, T 17.4%), discontinuations due to AEs (M 3.0%, T 2.6%), and deaths due to AEs (M 0.8%, T 0.8%). As of the 23Feb2020 safety update, 2 pts remain on M in Study 01, after 116 and 109 cycles (6.7 and 6.3 years), respectively. In Study 04, 16 pts (6%) continued on M, and 7 (2.6%) remained on T. Discussion M has demonstrated an acceptable safety profile across Phase 1, 2, and 3 studies. It has been administered for over 6 years without long-term cumulative safety issues. Combined M plus chemotherapy Q3W demonstrated acceptable safety and tolerability, similar to that for T plus chemotherapy Q3W in Study 04. Citation Format: Seock-Ah Im, Fatima Cardoso, Javier Cortes, Giuseppe Curigliano, Mark D. Pegram, Hope S. Rugo, Ursa Brown-Glaberman, Denise A. Yardley, Sung-Bae Kim, Maaike de Boer, Zbigniew Nowecki, Vesna Glavicic, Ido Wolf, Nele Claes, Joo Hyuk Sohn, Thomas Bachelot, Peter A. Kaufman, Jan Baughman, Shengyan Hong, Kenneth Jacobs, Edwin Rock, William J. Gradishar. Integrated safety summary of single agent and combination margetuximab in phase 1, 2, and 3 studies of HER2-positive advanced cancers and metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-12.

Background In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness of olaparib in similar patients, in a setting reflecting clinical practice. Methods This open-label, single-arm trial of olaparib (300 mg, twice daily) enrolled patients with BRCAm, HER2-negative mBC who had received taxane and/or anthracycline in the (neo)adjuvant/metastatic setting and not more than two lines of prior chemotherapy for mBC. Patients with hormone receptor–positive mBC had progressed on at least one line of endocrine therapy in an adjuvant/metastatic setting and were unsuitable for further endocrine treatment. This interim analysis was planned after 160 PFS events. Results Of 563 patients screened, 252 patients with gBRCAm were enrolled and received at least one dose of olaparib. The median investigator-assessed PFS was 8.11 months (95% confidence interval [CI], 6.93–8.67; 166/252 events [65.9% maturity]). The investigator-assessed clinical response rate was 48.6%, and median time to first subsequent treatment or death was 9.66 months (95% CI, 8.67–11.14). The most common treatment-emergent adverse events (TEAEs; >20% patients) were nausea, anaemia, asthenia, vomiting and fatigue. Eleven patients (4.4%) discontinued treatment because of a TEAE. Grade 3 or higher TEAEs occurred in 64 patients (25.4%), including anaemia (33 patients; 13.1%). Conclusion Olaparib was clinically effective in patients with gBRCAm, HER2-negative mBC with safety outcomes consistent with previous findings. ClinicalTrials.gov identifier: NCT03286842 .

BACKGROUND Intravenous trastuzumab, pertuzumab, and docetaxel is first-line standard of care for patients with HER2-positive metastatic breast cancer. Subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy has shown similar safety and tolerability to intravenous trastuzumab in patients with HER2-positive early and metastatic breast cancer; however, in the metastatic setting, this has yet to be shown globally.METHODS In this open-label, single-arm, multicenter phase 3b study, eligible patients were ≥18 years old with histologically/cytologically confirmed previously untreated HER2-positive metastatic breast cancer. All patients received ≥1 dose of subcutaneous trastuzumab (fixed-dose 600 mg) plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance dose: 420 mg/kg) and docetaxel (≥6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy.RESULTS At clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia. The most common grade ≥3 adverse events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%.CONCLUSIONS Efficacy/safety results of subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in metastatic breast cancer are consistent with historical evidence of intravenous trastuzumab. These findings further support the body of evidence indicating that subcutaneous administration does not affect the safety and efficacy profile of trastuzumab in HER2-positive breast cancer. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02402712 (date of registration: 30th March 2015)

Summary Background A subcutaneous formulation of pertuzumab and trastuzumab with recombinant human hyaluronidase in one ready-to-use, fixed-dose combination vial (pertuzumab, trastuzumab, and hyaluronidase-zzxf) was approved by the US Food and Drug Administration (FDA) on June 29, 2020. We report the primary analysis of the FeDeriCa study, which was designed to assess the pharmacokinetics, efficacy, and safety of the fixed-dose subcutaneous formulation compared to intravenous pertuzumab plus trastuzumab in patients with HER2-positive early breast cancer in the neoadjuvant–adjuvant setting. Methods FeDeriCa, a randomised, open-label, international, multicentre, non-inferiority, phase 3 study, was done across 106 sites in 19 countries. Patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1, HER2-positive, operable, locally advanced, or inflammatory stage II–IIIC breast cancer, and a left ventricular ejection fraction of 55% or more were randomly assigned (1:1), using a voice-based or web-based response system, to receive intravenous pertuzumab (840 mg loading dose, followed by 420 mg maintenance doses) plus intravenous trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg maintenance doses) or the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (1200 mg pertuzumab plus 600 mg trastuzumab loading dose in 15 mL, followed by 600 mg pertuzumab plus 600 mg trastuzumab maintenance doses in 10 mL), both administered every 3 weeks with neoadjuvant chemotherapy. Patients were stratified by hormone receptor status, clinical stage, and chemotherapy regimen. The investigator selected one of the two protocol-approved standard chemotherapy regimens before randomisation. Four cycles of HER2-targeted therapy were administered concurrently with the taxane. After surgery, patients continued the HER2-targeted therapy to receive an additional 14 cycles (total of 18). The primary endpoint was non-inferiority of the cycle 7 pertuzumab serum trough concentration (Ctrough; ie, cycle 8 predose pertuzumab concentration) within the fixed-dose combination for subcutaneous injection versus intravenous pertuzumab plus trastuzumab in the per-protocol pharmacokinetic population (all enrolled patients who adhered to prespecified criteria for pharmacokinetic assessment). Non-inferiority was concluded if the lower bound of the 90% CI of the geometric mean ratio was 0·8 or higher. The safety population included all patients who received at least one dose of study medication, including chemotherapy or HER2-targeted therapy. Enrolment, neoadjuvant therapy, and surgery have been completed; adjuvant treatment and follow-up are ongoing. The trial is registered with ClinicalTrials.gov, NCT03493854. Findings Between June 14, 2018, and Dec 24, 2018, 252 patients were randomly assigned to the intravenous infusion group and 248 to the fixed-dose combination group. The geometric mean ratio of pertuzumab serum Ctrough subcutaneous to serum Ctrough intravenous was 1·22 (90% CI 1·14–1·31). The most common grade 3–4 adverse events occurring during neoadjuvant treatment with HER2-targeted therapy plus chemotherapy in 5% or more of patients were neutropenia (34 [13%] of 252 patients in the intravenous infusion group vs 35 [14%] of 248 patients in the fixed-dose combination group), decreased neutrophil count (31 [12%] vs 27 [11%]), febrile neutropenia (14 [6%] vs 16 [6%]), diarrhoea (12 [5%] vs 17 [7%]), and decreased white blood cell count (18 [7%] vs nine [4%]). At least one treatment-related serious adverse event was reported in 25 (10%) patients in the intravenous infusion group and 26 (10%) patients in the fixed-dose combination group. One patient in each treatment group had an adverse event that led to death (urosepsis in the intravenous infusion group and acute myocardial infarction in the fixed-dose combination group); neither death was related to HER2-targeted therapy. Interpretation The study met its primary endpoint: the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection provides non-inferior cycle 7 pertuzumab serum Ctrough concentrations to intravenous pertuzumab plus trastuzumab in the neoadjuvant setting with comparable total pathological complete response rates, supporting the FDA approval. Safety was similar between treatment groups, and in line with other pertuzumab, trastuzumab, and chemotherapy trials. Follow-up is ongoing for long-term outcomes, including efficacy and long-term safety. Funding F Hoffmann-La Roche and Genentech.

Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I: 47% vs 24.5% in noncarriers), but there was no significant difference in the regional nodal status (58.5–63% with cN0). Contralateral breast cancer developed in 26.5% of BRCA1/2 mutation carriers and in 14% of noncarriers. Other primary cancers were also slightly more common in BRCA1/2 mutation carriers (16.5% vs 9.5%). The performed analysis did not show any significant differences between the groups in recurrence-free survival (p=0.312). There was no significant difference between patients with or without BRCA1/2 mutation as regards overall survival (p=0.649) and the risk of TNBC death (p=0.333). The survival from detection of metastases was similar in two groups (p=0.865). Our study demonstrated that the BRCA1 mutation does not affect TNBC patients’ outcomes.

Background: Pembrolizumab monotherapy showed durable antitumour activity and manageable safety in patients with metastatic triple-negative breast cancer. We aimed to examine whether the addition of pembrolizumab would enhance the antitumour activity of chemotherapy in patients with metastatic triple-negative breast cancer. Methods: In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurrent inoperable or metastatic triple-negative breast cancer using a block method (block size of six) and an interactive voice-response system with integrated web-response to pembrolizumab (200 mg) every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) or placebo plus chemotherapy. Randomisation was stratified by type of on-study chemotherapy (taxane or gemcitabine–carboplatin), PD-L1 expression at baseline (combined positive score [CPS] ?1 or, Breast Cancer Research Foundation, BCRF; Pfizer; AstraZeneca; Merck; Roche; Samsung; Merck Sharp and Dohme, MSD; Eisai, JC reports personal fees and research funding paid to his institution from Roche, AstraZeneca, Merck Sharp & Dohme, and Eisai; personal fees from Celgene, Cellestia, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, GlaxoSmithKline, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Kyowa Kirin, Novartis, Pfizer, Samsung Bioepis; research funding paid to his institution from Ariad Pharmaceuticals, Bayer Healthcare, F Hoffman-La Roche, Guardanth Health, Piqur Therapeutics, Puma C, and Queen Mary University of London, outside the submitted work. In addition, JC has a MedSIR patent pending. DWC reports research support from Merck during the conduct of the study; research support paid to his institution from Merck, Pfizer, and GlaxoSmithKline; personal fees from Merck, Roche–Genentech, AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Puma, Agenda, Exact Sciences, and Dynamo Therapeutics, outside the submitted work. In addition, DWC has a Biomarkers of TTK inhibitors patent pending. HSR reports funding for sponsored studies paid to the University of California San Francisco from Pfizer, Novartis, Lilly, Roche–Genentech, Macrogenics, OBI, Merck, Eisai, Immunomedics, Daiichi Sankyo, Seattle Genetics, and Odonate; travel support for educational meetings from Daiichi Sankyo, Mylan, Pfizer, Merck, AstraZeneca, Novartis, and Macrogenics; and consulting fees from Samsung and Puma, outside the submitted work. S-AI reports grants from AstraZeneca, Eisai, Pfizer, Roche, and Daewoong; an advisory role for AstraZeneca, Amgen, Eisai, Hanmi, Novartis, Lily, MedPacto, Pfizer, and Roche; and travel expenses for presentation from Novartis, outside the submitted work. CG reports Advisory Board fees from Merck Sharp & Dohme and Roche; and speaker's bureau fees from Bristol Myers Squibb and AstraZeneca, outside the submitted work. CHB reports grants and fees from Merck Sharp & Dohme for clinical research consulting during the conduct of the study; consulting–advisory role fees from Boehringer Ingelheim, GlaxoSmithKline, and Bayer; consulting–advisory role fees and grants for clinical research from Novartis, Pfizer, Roche–Genentech, Eisai, Merck Sharp & Dohme, and AstraZeneca; grants for clinical research from Abbvie, Amgen, Astellas Pharma, Bristol Myers Squibb, Celgene, Covance, Lilly, Medication, Merck Serono, and PharmaMar; grants for academic research projects from CPO, Pontificia Universidade Católica do Rio Grande do Sul, Latin American Cooperative Oncology Group, Grupo Brasileiro Estudos Câncer Mama, and Instituto Nacional de Câncer-Brazil, outside the submitted work. HI reports a grant from Merck Sharp & Dohme during the conduct of the study; honoraria and consulting fees from Novartis, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Eisai, and Chugai; and a grant from Chugai, outside the submitted work. NM reports honoraria and research funding paid to his institution from Chugai, AstraZeneca, Pfizer, Eli-Lilly, Eisai, Takeda, Kyowa-Kirin, Merck Sharp & Dohme, Novartis, and Daiichi Sankyo, outside the submitted work. EG reports non-financial support from Merck Sharp & Dohme during the conduct of the study; honoraria, consulting–advisory fees and meeting support from Novartis, Roche, Bristol Myers Squibb, and Pfizer; and honoraria from AstraZeneca and Astellas, outside the submitted work. SL reports research funding or consulting fees paid to her institution from Bristol Myers Squibb, Roche–Genentech, Puma Biotechnology, Pfizer, Seattle Genetics, Novartis, Merck Sharp & Dohme, Eli Lilly, Aduro Biotech, GI Therapeutics, AstraZeneca, and GlaxoSmithKline; and non-remunerated consultancy for Bristol Myers Squibb, Roche–Genentech, Pfizer, Seattle Genetics, Novartis, Merck Sharp & Dohme, and AstraZeneca, outside the submitted work. In addition, SL is supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York. ZG, JZ, GA, and VK are employees of Merck Sharp & Dohme and own stock or stock options in Merck. PS reports consultancy fees from Pfizer, AstraZeneca, Novartis, Roche, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Eisai, Celgene, and Puma; consultancy fees to his spouse from Genentech and Roche; and grants or funding to his institution from Roche, Genentech, Oncogenex, Novartis, Astellas, and AstraZeneca, outside the submitted work. All other authors declare no competing interests., The authors thank the patients, their families and caregivers for participating in this trial, all of the investigators and site personnel, and the following employees of Merck Sharp & Dohme: Wilbur Pan, Deborah Card, Eleanor Readinger, Shana Hamm, Roger Maxwell, and Krystal Bourdon, for collection of data, supervision of research, provision of study materials or patients or administrative or logistical support; Aline Galvao, for collection of data, supervision of research, administrative or logistical support, and review of imaging data related to the primary end point; Donna Letizia, for collection of data and imaging expertise; Jennifer Kimmel, for study management; Mercedes Bustamante, for data collection and management; Xuan Zhou and Madhusudhan Reddy Papasani, for statistical expertise; Christine McCrary Sisk, for medical writing and editorial assistance; and Joseph C Naggar and Michele McColgan, for administrative or logistical support.

Aim: This was to assess the treatment outcomes of ductal carcinoma of the breast (DCIS) based on the Van Nuys Prognostic Index. Material and Methods: 634 consecutive patients with DCIS were treated at the Warsaw Cancer Center, Poland between 1996 and 2008 based on the VNPI score. Tumorectomy without radiotherapy (T) was performed in 123 (20%) patients, breast conserving treatment (BCT) in 206 (32%) and mastectomy (M) in 305 (48%). Disease-free survival (DFS) and overall survival (OS) were analysed within 3 groups and a multivariate analysis was performed to determine the most important factor affecting local relapse. Results: 5-year, 10-year and 15-year DFS in the M group were respectively 98%, 97% and 97% whilst 5-year, 10-year and 15-year DFS in the BCT group were respectively 91%, 87% and 80%. 5-year, 10-year and 15-year DFS in the T group were respectively 92%, 73% and 67%. Local recurrence was observed in 54 patients. In 40% cases this was noninvasive and in 60 % invasive. Only 4 of 54 patients with recurrence died due to breast cancer. 5-year, 10-year and 15-year OS in the M group were respectively 96%, 92% and 89%. 5-year, 10-year and 15-year OS in the BCT group were respectively 99%, 94% and 85%. 5-year, 10-year and 15-year OS in the T group were respectively 95%, 90% and 73% (p=0.422). Tumor size assessed by mammography was the only variable affecting DFS. Conclusions: Treatment outcomes of DCIS based on the Van Nuys Prognostic Index are comparable with those cited the literature, however, the recurrence rate in the T group seems to be very high. This group requires that new risk factors be sought for prior to taking a treatment decision. Citation Format: Niwinska A, Galecki J, Nagadowska M, Piechocki J, Kunkiel M, Jagiello-Gruszfeld AI, Nowecki Z. Evaluating the significance of the Van Nuys prognostic index for the management of ductal carcinoma in situ – one center's experience [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-12.

AIM: To assess those factors which affect survival in three groups of breast cancer patients with leptomieningeal metastasis (LM) treated at the Warsaw Cancer Center in Poland. Subject groups were: 187 patients consecutively referred during 2003-2015 (group A), 69 patients with LM as the first/only site of dissemination of the disease (group B) and 27 patients who survived for more than 1 year (group C). Methods: Univariate and Cox multivariate analysis were performed using the following variables: age, Karnofsky Performance Status (KPS), biological subtype of breast cancer (ER/PR+HER2- vs. HER2+ vs. ER-PR-HER2-), systemic intravenous/oral treatment, intrathecal treatment, radiation therapy and the number of treatment methods. Results. Median survival of patients in group A was 17 weeks, in group B 18 weeks (p=0.72) and in group C 19.2 months. In group A, factors positively affecting survival were: KPS => (p=0.01), older age (p=0.003), biological subtype ER/PR+HER2- (p=0.003), systemic intravenous/oral treatment (p=0.0001), intrathecal treatment (p=0.001) and radiation therapy (p=0.001). In the group B, the most important factors affecting survival were a KPS=> 70 (p=0.001), biological subtype ER/PR+HER2- (p=0.04), systemic therapy (p=0.001) and intrathecal therapy (p=0.001). For group C, older patients (p=0.01) with ER/PR+HER2- breast cancer (p=0.05, HR 0.18) and after systemic intravenous/oral treatment (p=0.02) had higher a probability of survival after 1 year. Conclusions: Those breast cancer LM patients who were older, having high KPS, with luminal breast cancer and treated with systemic inravenous/oral therapy had a higher probability of survival than the rest of the group. Based on the presented data, the role of intrathecal therapy could not be exactly defined. Citation Format: Niwinska A, Rudnicka H, Kunkiel M, Jagiello-Gruszfeld A, Nowecki Z. Analysing the factors affecting survival of breast cancer patients with leptomeningeal metastasis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-07.

Background Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8mg/kg loading dose, then 6mg/kg every 3weeks (q3w)] and pertuzumab (840mg loading dose, then 420mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54years; 29% had received prior trastuzumab. Median treatment duration was 16months for pertuzumab and trastuzumab and 4months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9–22.7] months overall (19.6, 23.0 and 18.1months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%–82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). Conclusions Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. ClinicalTrials.gov NCT01572038.

1023 Background: Chemotherapy with immune checkpoint inhibitors can improve outcomes vs chemotherapy alone in patients (pts) with metastatic TNBC; however, many still have poor clinical outcomes. BEGONIA is an ongoing 2 part, multicenter, multiarm, open-label platform study evaluating safety and efficacy of D (anti–PD-L1)+P and D±P combined with novel therapies as first-line (1L) treatment for metastatic TNBC (NCT03742102). We report initial results from Part 1 of Arm 1, D+P, and Arm 6, D+T-DXd, an antibody-drug conjugate comprising an anti-HER2 antibody, tetrapeptide-based cleavable linker, and topoisomerase I inhibitor payload. Methods: Eligible pts had untreated unresectable locally advanced or metastatic TNBC. Pts with HER2-low–expressing tumors (IHC 2+/ISH–, IHC 1+/ISH–, or IHC 1+/ISH untested) per local testing were assigned to the D+T-DXd arm. Pts received D (1500 mg IV Q4W)+P (90 mg/m2 IV Day 1, 8, 15 Q4W) in Arm 1 and D (1120 mg IV)+T-DXd (5.4 mg/kg IV) Q3W in Arm 6, until progression or unacceptable toxicity. Primary objectives are safety and tolerability. Secondary endpoints include objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS). Tumors were assessed Q8W (D+P) or Q6W (D+T-DXd). The first 6 pts treated with D+T-DXd were evaluated for dose-limiting toxicities (DLTs), with additional pts enrolled if D+T-DXd was tolerated. Study arms are noncomparable due to differing eligibility criteria, treatments, and data maturity. Results: Arm 1 D+P (data cutoff Sep 2020): 23 pts received D+P (7 ongoing); 2 discontinued D+P due to AEs. Median follow-up time was 16.6 (range 8.5–19.8) mos. Any Grade 3/4 AEs and SAEs were experienced by 10 (44%) and 1 (4%) pts, respectively. D dose was delayed for 7 (30%) pts. Confirmed ORR was 13/23 (57%) with 54% of those remaining in response at 12 mos (median DoR not reached). Median PFS was 7.3 (95% CI 5.4–13.8) mos in the D+P arm. Arm 6 D+T-DXd (data cutoff Nov 2020): 11 pts received D+T-DXd to date (all ongoing). Median follow-up time was 2.3 (0–6) mos. Any Grade 3/4 AEs and SAEs were experienced by 4 (36%) and 1 (9%) pts, respectively. Pts who received D+T-DXd had no DLTs and 1 had a Grade 1 troponin increase. D dose was delayed and T-DXd dose reduced for 2 (18%) pts each. Confirmed ORR was 4/4 (100%; only 4 pts had the opportunity to complete 2 on-treatment disease assessments) with all 4 remaining in response at data cutoff (median DoR not reached). Conclusions: D+P demonstrated a tolerable safety profile and response rate as expected for a 1L TNBC IO/taxane combination. D+T-DXd showed promising early safety and efficacy in 1L HER2-low–expressing TNBC; pt evaluation and enrollment for D+T-DXd are ongoing. D+T-DXd data will be updated and the impact of PD-L1 expression in both arms will be examined. Clinical trial information: NCT03742102 .

e12566 Background: This study discusses the analysis of the prospectively collected material on pregnant patients treated for breast cancer at the Department of Breast Cancer and Reconstructive Surgery of the Maria Skłodowska-Curie National Oncology Institute - National Research Institute (until 2020: Oncology Center - Institute) in Warsaw, in the years 1995 - 2020. 84 patients were included into the final analysis and 72 children were assessed simultaneously. Methods: The paper summarizes information on the diagnosis and treatment of breast cancer during pregnancy, the course of pregnancy and childbirth and the birth parameters of children i.e. weight, length and Apgar score, as well as the dependencies between them, mainly the impact of some breast cancer, diagnosis and treatment process features on the newborns. The patietnt’s survavial - DFS ( disease free survival) and OS ( overall survival) - was also analyzed. The course of breast cancer diagnosis and treatment data were obtained from the patients’ medical documentation (medical records) and from information provided by the mothers during follow-up visits and read in the children's health books. In order to answer the research questions, statistical analyzes were conducted using the IBM SPSS Statistics 26 package. Results: In the analyzed period, the disease recurrence was recognized in 34 (40.5%) patients, and 24 (28.6%) patients died. The median disease-free survival (DFS) was 12.3 years (147.5 months), and the median overall survival (OS) was not reached during the follow-up period. The estimated 5-year survival rates for DFS and OS were 57.9% and 74.5% respectively, and for 10-year survival - 51.4% and 64.5%. The study showed a statistically significant relationship between the baseline clinical advancement and DFS. It has been also analyzed how the diagnosis, treatment and method of pregnancy termination changed in two time periods (1995-2012 and 2013-2020). There were no statistically significant differences in survival - both DFS and OS - between the group of patients treated before and after 2012. In the assessment of the impact of some factors on the birth children parameters (weight and length), statistically significant results were obtained for: pregnancy advancement at diagnosis, breast cancer stage at diagnosis, pregnancy advancement at the start of chemotherapy, the chemotherapy regimen (classic or dose-dense), the number of cycles of chemotherapy given during pregnancy, and the number of drugs used in supportive treatment. Conclusions: The entire analysis has become not only an insightful characteristic of the studied group, but also these results may be important in everyday clinical practice and may help to optimize the management of an extremely complex and difficult situation, which is the coexistence of pregnancy with a malignant disease that threatens the mother’s life.

e13015 Background: The switch of anti-HER2 therapy from the reference drug Herceptin to a biosimilar has presented challenges to the clinics. Real world data on trastuzumab biosimilars are very limited or not available. In our clinic we perform observational retrospective study to confirm safety and efficacy Kanjinti. Methods: 195 patients (pts) with HER2-positive breast cancer were treated with Kanjinti from Jul.18. 2018 to Jan.29.2020. Cardiac events (↓LVEF) and other unexpected or serious adverse events were monitored in all pts. 34 pts received carboplatin, docetaxel pertuzumab and trastuzumab biosimilar in neoadjuvant setting, 99 received trastuzumab biosymilar in monotherapy or with other cytostatic drugs in neoadjuvant or adjuvant setting, and 62 received docetaxel, pertuzumab and Kanjinti in metastatic setting. Results: Pertuzumab was used in combination with Kanjinti in 49% of pts (32% in the 1st. line of palliative tretment and 17% in the neoadjuvant settings, respectively).Switching from Herceptin to Kanjinti was observed in 65% of MBC patients and 37% of EBC patients. Switching was done at a median of 4th cycle. 6 patients had a decline in LVEF. No other trastuzumab related adverse events was observed. Conclusions: The management of HER2 positive breast cancer in our clinic follows the international recommendations. This is the first real world safety data of Kanjinti from Poland. The 12-month follow-up treatment with Kanjinti an acceptable cardiac safety profile. In cases where there was a switch from Herceptin to Kanjinti or Kanjinti combined with pertuzumab, the safety profile was similar to that previously reported in other studies.

e13070 Background: Patients with metastatic breast cancer can derive clinical benefit from several subsequent lines of chemotherapy. However, in heavily pre-treated patients, agents with clinical activity, a favourable side effects profile and a convenient administration modality are preferred. Oral etoposide may be an interesting treatment option in this group of patients. Methods: This was a retrospective observational study performed in single institution in 22 patients with MBC refractory to prior anthracycline, taxane, and capecitabine therapy. All patients were treated with oral etoposide at 50 mg/day on days 1-20. Treatment cycles were repeated every 28 days. Results: The median age were 53 years (42-68). The median number of previous chemotherapy lines was 5 (range 2-7). There were no complete or partial responses. Median PFS was 7 months. In 5 patients, the disease stabilized for over 12 months. Interestingly, etoposide activity was unrelated to the number of previous lines and type of metastatic involvement. Oral etoposide was well tolerated with only one patients discontinuing therapy due to toxicity. Conclusions: In real practice oral etoposide is a valuable and safe option for pre-treated metastatic breast cancer patients and might be considered in patients failing other approaches, but still suitable for chemotherapy.

Background: Pembrolizumab (pembro) monotherapy showed durable antitumor activity and manageable safety in patients (pts) with metastatic triple-negative breast cancer (TNBC) in the KEYNOTE-012, -086, and -119 studies. In a prespecified interim analysis of KEYNOTE-355 (NCT02819518), pembro combined with chemotherapy (chemo) showed a statistically significant improvement in PFS versus chemo alone in pts with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 CPS ≥10 (HR for progression or death, 0.65, 95% CI, 0.49-0.86; one-sided P=0.0012 [prespecified statistical criterion was alpha=0.00411 at this interim analysis]). Additionally, pembro + chemo was generally well tolerated, with no new safety signals. Here, we examine PFS outcomes for each chemo partner and present key secondary endpoints from KEYNOTE-355. Methods: 847 pts with measurable disease per RECIST v1.1, ECOG PS 0-1, and ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel 100 mg/m2 days 1, 8, and 15 every 28 days; paclitaxel 90 mg/m2 days 1, 8, and 15 every 28 days; or gemcitabine 1000 mg/m2 + carboplatin AUC 2 days 1 and 8 every 21 days) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Steroid premedication for paclitaxel was given according to local guidelines and practices, and was not restricted by the protocol. Crossover between arms was not allowed. Pts were stratified by chemo type (taxane vs gemcitabine/carboplatin), PD-L1 status (CPS ≥1 vs Results: As of Dec 11 2019, median follow-up was 25.9 mo for pembro + chemo (n=566) and 26.3 mo for pbo + chemo (n=281). The HR for PFS favored pembro regardless of choice of chemo or CPS population (Table). Results for the key secondary endpoints of ORR, DCR, and DOR favored pembro + chemo, with the treatment effect increasing as CPS increased (Table). Conclusion: In subgroup analysis, PFS with pembro + chemo compared to pbo + chemo in pts with metastatic TNBC was improved regardless of chemo partner. A trend toward improved efficacy with PD-L1 enrichment with pembro + chemo was observed for ORR, DCR and DOR endpoints. These data further support the potential of pembro + chemo as a first-line treatment option for metastatic TNBC. CPS ≥ 10CPS ≥ 1All ptsPembro + ChemoPbo + ChemoPembro + ChemoPbo + ChemoPembro + Chemo|Pbo + ChemoN = 220N = 103N = 425N = 211N = 566N = 281PFS, mo median (95% CI)9.7 (7.6 - 11.3)5.6 (5.3 - 7.5)7.6 (6.6 - 8.0)5.6 (5.4 - 7.4)7.5 (6.3 - 7.7)5.6 (5.4 - 7.3)HR (95% CI)0.65 (0.49 - 0.86)0.74 (0.61 - 0.90)0.82 (0.69 - 0.97)PFS by on-study chemo, (n [%)) mo median(95% CI)Nab-Paclitaxel(63 [28.6%]) 9.9(36 [35.0%]) 5.5(130 [30.6%]) 6.3(74 [35.1%)) 5.3(173 [30.6%]) 7.5(95 [33.8%]) 5.4HR (95% CI)0.57 (0.34 - 0.95)0.66 (0.26 - 0.82)0.69 (0.51 - 0.93)Paclitaxel(33 [15.0%]) 9.6(11 [10.7%]) 3.6(62 [14.6%]) 9.4(22 [10.4%]) 3.8(82 [14.5%]) 8.0(32 [11.4%]) 3.8HR (95% CI)0.33 (0.14 - 0.76)0.46 (0.26 - 0.82)0.57 (0.35 - 0.93)Gemcitabine-Carboplatin(124 [56.4%]) 8.0(56 [54.4%]) 7.2(233 [54.8%]) 7.5(115 [54.5%]) 7.5(311 [54.9%]) 7.4(154 [54.8%]) 7.4HR (95% CI)0.77 (0.53 - 1.11)0.86 (0.66 - 1.11)0.93 (0.74 - 1.16)ORR, % (95% CI)53.2 (46.4 - 59.9)39.8 (30.3 - 49.9)45.2 (40.4 - 50.0)37.9 (31.3 - 44.8)41.0 (36.9 - 45.2)35.9 (30.3 - 41.9)DCR, % (95% CI)65.0 (58.3 - 71.3)54.4 (44.3 - 64.2)58.6 (53.7 - 63.3)53.6 (46.6 - 60.4)56.0 (51.8 - 60.1)51.6 (45.6 - 57.6)DOR, mo, median (range)19.3 (1.6+ - 29.8)7.3 (1.5 - 32.5+)10.1 (1.0+ - 29.8)6.5 (1.5 - 32.5+)10.1 (1.0+ - 29.8)6.4 ( 1.5 - 32.5+)"+" indicates there is no progressive disease by the time of last disease assessment. Citation Format: Hope S. Rugo, Peter Schmid, David W. Cescon, Zbigniew Nowecki, Seock-Ah Im, Mastura Md Yusof, Carlos Gallardo, Oleg Lipatov, Carlos Henrique Barrios, Jose Perez-Garcia, Hiroji Iwata, Norikazu Masuda, Marco Torregroza Otero, Erhan Gokmen, Sherene Loi, Zifang Guo, Jing Zhao, Vassiliki Karantza, Gursel Aktan, Javier Cortes. Additional efficacy endpoints from the phase 3 KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-01.

Background: Pembrolizumab monotherapy did not significantly improve overall survival (OS) as second- or third-line treatment for metastatic TNBC vs chemotherapy in the randomized, open-label, phase 3 KEYNOTE-119 study (NCT02555657; N = 622). However, the benefit of pembrolizumab compared with chemotherapy appeared to be greater with increasing PD-L1 expression as quantified by combined positive score (CPS; defined as the number of PD-L1–staining cells [tumor cells, lymphocytes, macrophages] divided by the total number of viable tumor cells, multiplied by 100). In the current exploratory analysis, we aimed to determine whether expression of PD-L1 on tumor cells contributes to the value of PD-L1 as a predictive biomarker in metastatic TNBC.Methods: Patients with centrally confirmed TNBC and 1 or 2 prior systemic treatments for metastatic disease were enrolled in KEYNOTE-119. Patients were randomly assigned 1:1 to pembrolizumab 200 mg Q3W or investigator’s choice of single-agent chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). PD-L1 expression in tumor samples was assessed using PD-L1 IHC 22C3 pharmDx and quantified per tumor proportion score (TPS; defined as the percentage of PD-L1–expressing tumor cells [partial or complete membrane staining] relative to total number of tumor cells) and CPS. Quantitative immune cell density (QID) was defined as CPS minus TPS. QID isolates immune cells but may be truncated when TPS is high. The ability of each scoring method (TPS, CPS, and QID) to predict objective response rate (ORR) with pembrolizumab, including receiver operating characteristics (ROC) analysis, and OS hazard ratios (HRs; pembrolizumab vs chemotherapy) was evaluated.Results: Tumor samples were available for 601 patients (pembrolizumab, 309; chemotherapy, 292) in KEYNOTE-119. ORR was 9.7% (30/309) with pembrolizumab and 11.3% (33/292) with chemotherapy when PD-L1 expression status was not considered. In the pembrolizumab arm, the area under the ROC curve (AUROC; 95% CI) was 0.69 (0.58-0.80) for tumor samples scored for CPS, 0.66 (0.55-0.77) for QID, and 0.55 (0.46-0.64) for TPS. ROC analysis is shown in the Table. At each cutoff, QID had lower estimated sensitivity (ie, missed responders) and a lower Youden Index compared with CPS. The number of missed responders (of 30 total in the pembrolizumab arm) for QID relative to CPS were 2, 5, 5, 6, 2, and 2 at cutoffs of 1, 10, 20, 30, 40, and 50, respectively. Across all practical cutoffs, the OS HR tended to be slightly smaller for CPS than QID. At cutoffs corresponding to the upper percentiles of 10, 20, 40, and 60, OS HRs were 0.497, 0.658, 0.758, and 0.850, respectively, for CPS vs 0.572, 0.712, 0.814, and 0.863, respectively, for QID. QID appeared to be orthogonal to TPS (r = -0.03 for all 601 observations; r = -0.04 after eliminating 7 potentially truncated values).Conclusions: Trends estimated using KN119 suggest that tumor cell expression is an important component of PD-L1 as a predictive biomarker of pembrolizumab efficacy in metastatic TNBC. In this exploratory analysis, when immune cells alone were used to measure PD-L1 expression, a meaningful number of responders was missed and OS benefit trended toward higher HR estimates. Tumor and immune cell PD-L1 expression may represent distinct (presumably negative modulatory) mechanisms. Table. ROC AnalysisCutoffCPS SensCPS SpecCPS YICPS PrevQID SensQID SpecQID YIQID PrevTPS SensTPS SpecTPS YITPS Prev010011001100110.8330.3660.1990.6540.7670.4160.1820.6020.3000.7890.0890.220100.5670.7170.2840.3110.4000.8140.2140.2070.2000.8920.0920.117200.5000.8490.3490.1840.3330.9250.2580.1000.1670.9320.0990.078300.3670.8920.2590.1330.1670.9570.1240.0550.1000.9430.0430.061400.2000.9350.1350.0780.1330.9860.1190.0260.0670.9530.0200.049500.2000.9570.1570.0580.1330.9930.1260.0190.0670.9680.0340.036 Citation Format: Eric P. Winer, Oleg Lipatov, Seock-Ah Im, Anthony Goncalves, Eva Muñoz-Couselo, Keun Seok Lee, Zbigniew Nowecki, Peter Schmid, Kenji Tamura, Laura Testa, Isabell Witzel, Shoichiro Ohtani, Stephanie Hund, Karina Kulangara, Vassiliki Karantza, Jaime A. Mejia, Junshui Ma, Petar Jelinic, Lingkang Huang, Kenneth Emancipator, Javier Cortes. Contribution of tumor and immune cells to PD-L1 as a predictive biomarker in triple-negative breast cancer (TNBC): Analysis from KEYNOTE-119 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD14-04.

Objectives: The key objectives of CONTESSA are to evaluate the efficacy and safety of tesetaxel plus a reduced dose of capecitabine as an all-oral regimen versus capecitabine alone in patients with HER2-, HR+ MBC previously treated with a taxane. Rationale: Tesetaxel is a novel, oral taxane with several properties that make it unique, including: oral administration with a low pill burden; a long (8-day) terminal plasma half-life in humans, enabling infrequent, once-every-3 weeks (Q3W) dosing; no observed hypersensitivity reactions; and significant activity against chemotherapy-resistant breast cancer cell lines. More than 1,000 patients have been treated with tesetaxel in clinical studies. Tesetaxel had encouraging monotherapy activity in a Phase 2 study in 38 patients with HER2-, HR+ MBC, with a confirmed objective response rate (ORR) per RECIST 1.1 of 45% and median progression-free survival (PFS) of 5.4 months (Seidman et al, 2018 ASCO Annual Meeting). Methodology: CONTESSA is a multinational, multicenter, randomized (1:1), Phase 3 registration study comparing tesetaxel (27 mg/m2 on Day 1 of a 21-day cycle) plus a reduced dose of capecitabine (1,650 mg/m2/day on Days 1-14 of a 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day on Days 1-14 of a 21-day cycle) in patients with HER2-, HR+ MBC who have received no more than one chemotherapy regimen for advanced disease and have received a taxane in the (neo)adjuvant setting. There was no restriction on the disease-free interval following taxane therapy. The primary endpoint is PFS assessed by an Independent Radiologic Review Committee (IRC). CONTESSA was designed with 90% power to detect a 2.5-month improvement in median PFS (HR=0.71). Secondary endpoints are overall survival (OS), ORR and disease control rate. Results: CONTESSA, which enrolled 685 patients, met the primary endpoint of improved PFS as assessed by the IRC. Median PFS was 9.8 months for tesetaxel plus a reduced dose of capecitabine versus 6.9 months for capecitabine alone, an improvement of 2.9 months [HR=0.716 (95% CI: 0.573-0.895); p=0.003]. ORR was 57% for tesetaxel plus a reduced dose of capecitabine versus 41% for capecitabine alone (p=0.0002). OS data are immature. Tesetaxel plus capecitabine was associated with a manageable side effect profile consistent with previous clinical studies. Grade ≥3 treatment-emergent adverse events (TEAEs) that occurred in ≥5% of patients (tesetaxel plus capecitabine vs. capecitabine alone) were: neutropenia (71.2% vs. 8.3%); diarrhea (13.4% vs. 8.9%); hand-foot syndrome (6.8% vs. 12.2%); febrile neutropenia (12.8% vs. 1.2%); fatigue (8.6% vs. 4.5%); hypokalemia (8.6% vs. 2.7%); leukopenia (10.1% vs. 0.9%); and anemia (8.0% vs. 2.1%). TEAEs resulting in treatment discontinuation in ≥1% of patients (tesetaxel plus capecitabine vs. capecitabine alone) were: neutropenia or febrile neutropenia (4.2% vs. 1.5%); neuropathy (3.6% vs. 0.3%); diarrhea (0.9% vs. 1.5%); and hand-foot syndrome (0.6% vs. 2.1%). Treatment discontinuation due to any adverse event occurred in 23.1% of patients treated with tesetaxel plus capecitabine versus 11.9% of patients treated with capecitabine alone. Grade 2 alopecia occurred in 8.0% of patients treated with tesetaxel plus capecitabine versus 0.3% of patients treated with capecitabine alone. Grade ≥3 neuropathy occurred in 5.9% of patients treated with tesetaxel plus capecitabine versus 0.9% of patients treated with capecitabine alone. Conclusion: An all-oral regimen of tesetaxel plus a reduced dose of capecitabine significantly improved PFS versus capecitabine alone. Neutropenia was the most frequent Grade ≥3 TEAE. Rates of clinically significant alopecia and neuropathy were low. Citation Format: Joyce O'Shaughnessy, Lee Schwartzberg, Martine Piccart, Hope S. Rugo, Denise A Yardley, Javier Cortes, Michael Untch, Nadia Harbeck, Gail S. Wright, Igor Bondarenko, John Glaspy, Zbigniew Nowecki, Fadi Kayali, Arlene Chan, Christelle Levy, Mei-Ching Liu, Sung-Bae Kim, Julie Lemieux, Alexey Manikhas, Sara Tolaney, Elaine Lim, Andrea Gombos, Agostina Stradella, Mark Pegram, Peter Fasching, Laszlo Mangel, Vladimir Semiglazov, Veronique Dieras, Luca Gianni, Michael A Danso, Jeff Vacirca, Stew Kroll, Joseph O'Connell, Kevin Tang, Thomas Wei, Andrew Seidman. Results from CONTESSA: A phase 3 study of tesetaxel plus a reduced dose of capecitabine versus capecitabine alone in patients with HER2-, hormone receptor + (HR+) metastatic breast cancer (MBC) who have previously received a taxane [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-01.

Rak podstawnokomorkowy (BCC— basal cell carcinoma ) oraz rak kolczystokomorkowy (SCC — squamous cell carcinoma ) są najcześciej wystepującymi nowotworami zlośliwymi wystepującymi u osob rasy kaukaskiej. Pomimo ze rzadko prowadzą do powstawania przerzutow i zgonu chorego, to stanowią jednak bardzo istotny problem kliniczny, poniewaz charakteryzują sie naciekaniem i niszczeniem sąsiadujących tkanek i struktur, co sprawia, ze stają sie powodem powaznych defektow estetycznych i znacząco upośledzają jakośc zycia chorych. U pacjentow w trakcie przewleklej immunosupresji lub z genetyczną predyspozycją mogą miec jednak agresywny i prowadzący do śmierci przebieg. Z tego powodu Sekcja Onkologiczna Polskiego Towarzystwa Dermatologicznego oraz sekcja Akademia Czerniaka Polskiego Towarzystwa Chirurgii Onkologicznej, na podstawie aktualnych wytycznych europejskich, rekomendacji amerykanskich National Comprehensive Cancer Network (wersja 1.2015) oraz interwencyjnych recenzji publikacji opracowanych przez Cochrane Skin Group , podjela probe usystematyzowania zasad postepowania diagnostyczno-terapeutycznego oraz ustalenia jednorodnych zasad prewencji pierwotnej i wtornej u pacjentow z podejrzeniem/rozpoznaniem raka podstawnokomorkowego lub kolczystokomorkowego. W pracy przedstawiono aktualne zalecenia dotyczące rozpoznania i leczenia rakow skory, uwzgledniając korzyści oraz problemy z nim związane, a takze wytyczne monitorowania pacjentow po terapii.

500 Background: The standard of care for HER2-positive EBC is chemotherapy plus one year of HER2-directed therapy. However, recurrence—particularly in high-risk populations—remains a problem, as does systemic chemotherapy-associated toxicity. In KAITLIN, we aimed to improve efficacy and reduce toxicity by replacing taxanes and trastuzumab with T-DM1. Methods: KAITLIN (NCT01966471) is a phase 3, randomized, open-label study that enrolled 1846 patients with adequately excised, centrally confirmed HER2-positive EBC either node-positive (LN+); or node-negative, HR-negative, and tumor size > 2.0 cm. Within 9 weeks of surgery, patients were randomized 1:1 to 3-4 cycles of anthracycline-based chemotherapy followed by 18 cycles of T-DM1 3.6 mg/kg + pertuzumab 420 mg q3w (loading dose [LD] 840 mg) (AC-KP) or taxane (3-4 cycles) + concurrent trastuzumab 6 mg/kg (LD 8 mg/kg) + pertuzumab 420 mg q3w (LD 840 mg) (AC-THP). Patients were stratified by world region, nodal status, HR status, and anthracycline type. Adjuvant radiotherapy and/or endocrine therapy was administered after 4 cycles of HER2-targeted therapy when indicated. The co-primary endpoints were invasive disease-free survival (IDFS) in the LN+ and in the ITT populations applying a hierarchical testing procedure. Secondary endpoints included overall survival (OS), patient-reported outcomes (PROs), and safety. Results: KAITLIN did not meet its co-primary endpoints. In LN+ patients (n = 1658), there was no significant difference between arms in IDFS event risk (stratified hazard ratio = 0.97; 95%CI 0.71–1.32). Three-year IDFS was 94.1% with AC-THP and 92.7% with AC-KP. Results were similar in the ITT population (stratified hazard ratio = 0.98; 95%CI 0.72–1.32; 3-year IDFS: 94.2% vs 93.1%). OS data are immature with an event rate of ~4%–5% in each arm. During the study overall, there was a similar incidence of grade ≥3 AEs (55.4% vs 51.8%) and SAEs (23.3% vs 21.4%) with AC-THP and AC-KP, respectively. More patients receiving AC-KP than AC-THP discontinued T-DM1 or trastuzumab, respectively, because of AEs (26.8% vs 4.0%). PRO data will be presented. Conclusions: Replacing adjuvant taxane and trastuzumab with T-DM1 did not result in significantly improved efficacy or overall safety. Nonetheless, in this high-risk population, a favorable IDFS outcome was achieved in both study arms. HP + chemotherapy remains the standard of care for patients with high-risk HER2-positive EBC. Clinical trial information: NCT01966471 .

e12627 Background: Aurora A (AURKA) is serine/threonine kinase that plays a regulatory role in mitosis and multiple signaling pathways. Overexpression of AURKA has been found in many solid tumors including breast cancer. It also has been found to be a prognostic marker indicating resistance to taxane treatment and poor prognosis in ER positive breast cancer. The aim of this study is to assess clinical value of Aurora-A serum level determination in patients with breast cancer qualified for neoadjuvant chemotherapy. Methods: 60 patients with confirmed breast cancer before treatment were qualified for the study, aged 31-77 (median 52 years), including 30 premnopausal and 30 pomenopausal. The control group consisted of 30 healthy women aged 20-80 (median 53 years). Clinical and pathological features were determined in a selected group of patients with breast cancer who subsequently underwent preoperative chemotherapy, i.e. tumor size (T), lymph node status (N), presence of distant metastases (M), estrogen receptor status (ER) and progesterone (PgR), HER2 receptors and Ki 67 proliferative index. The blood serum of the examined patients and healthy women was determined by the enzyme-linked ELISA method in doublets of the AURKA biomarker concentration. Mann-Whitney test and ROC curve analysis were used for statistical calculations. Results: No significant differences were found between the concentrations of AURKA in breast cancer patients and in the control group. In both analyzed groups there were no significant differences in biomarker levels depending on the menopausal status. When assessing the relationship between AURKA concentrations and clinical-pathological features, significant differences were found depending on the state of the lymph nodes (N0 vs N1 + N2) (p = 0.006). There was no correlation between the concentrations of the tested biomarker and the tumor size (T), the state of receptors and the Ki67 index. In patients with a lack of receptors (triple negative vs others), higher levels of Aurora A (p = 0.06) in the blood serum were observed at the level of the statistical trend. Conclusions: The preliminary results obtained indicate the potential usefulness of determining the concentration of the new biomarker Aurora A in the blood serum of patients with breast cancer. The research is continuing.

e12620 Background: Preoperative neutrophil-lymphocyte ratio (NLR) have been suggested to be correlated with the prognosis of patients with breast cancer (BC). However, the results still remain controversial. The goal of our study was to evaluate the predictive and prognostic value of NLR in early stage triple negative and HER2-pos breast cancer patients undergoing NAC. Methods: 96 female patients (pts) with histologically proven breast cancer (51 TNBC, and 45 HER2 pos) were analysed in this retrospective analysis. The NLR before the initiation of NAC was documented. Histopathological response in surgically removed specimens was evaluated using the Residual Cancer Burden (RCB) Calculator (by MD Anderson Cancer Center). The pCR was defined as no invasive tumor in primary tumor bed and lymph nodes. The NLR variable was analyzed as both continuous and categorical. The impact on pCR and RCB was tested using Mann-Whitney, Kruskal-Willis or the Chi-2 test, respectively. Results: Only 4 categories of NAC were used: in TNBC 4 x ACdd followed by 12 x PCL (38 pts) or 4 x ACdd followed by 12 x PCL+ carboplatin AUC 1.0-2 (13 pts), in HER2-pos 39 pts received 6 x TCH (docetaxel + tratuzumab + carboplatin AUC 6) and 6 pts 4 x ACdd followed by 12 x PCL iv + 4 x trastuzumab. In 27 pts (53%) with TNBC and 24 pts (53%) with HER2-pos breast cancer pCR was obtained after NAC. RCB distribution was: 0-53.1%, 1-22%, 2-17.6%, 3-7.3%. No association with NLR and pCR could be observed (p > 0.26). No association with NLR and RCB could be observed (p > 0.18). Conclusions: In our retrospective analysis we could not demonstrate predictive or prognostic value of NLR in the cohort of early stage triple negative and HER2-positive breast cancer patients treated with NAC. Further studies are planned in a group of patients with Luminal B, HER2 – negative breast cancer, who received NAC.

1000 Background: Pembrolizumab (pembro) monotherapy showed promising antitumor activity and manageable safety in patients (pts) with metastatic TNBC in KEYNOTE-012, -086 and -119. KEYNOTE-355 (ClinicalTrials.gov, NCT02819518) compared pembro + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated locally recurrent inoperable or metastatic TNBC. Methods: Pts with ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel; paclitaxel; or gemcitabine/carboplatin) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Pts were stratified by chemo type (taxane vs gemcitabine/carboplatin), PD-L1 status (CPS ≥1 vs

e12655 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) for breast cancer predicts the risk of recurrence and increasingly may indicate the need for additional therapy postoperatively. Methods: A retrospective analysis was performed in two cohorts of patients (pts) treated with docetaxel, trastuzumab and carboplatin (TCH) or with docetaxel, carboplatin and dual blockade (TCH-P) in the neoadjuvant setting in patients with early breast cancer (tumor size < 50 mm and > 10 mm and cN0 or cN1) in our Clinic, and who had definitive surgery was conducted. Demographic data, size, grade, tumor type, receptor status prior to neoadjuvant treatment, pathological complete response (pCR) rates, and adverse effects were analyzed. The pCR was defined as ypT0 ypN0. Results: Patient in cohort A (n = 58) received TCH x 6 cycles and in cohort B (n = 25) TCH-P x 6 cycles. Median age was 51 (range 23 to 76 years) in cohort A and 46 (range: 30-68) in cohort B. In cohort A 37 (64%) of pts was HR-positive, in cohort B only 9 (36%) pts . The most common adverse events in both groups were neutropenia, diarrhea, chemotherapy induced polyneuropathy and febrile neutropenia. There are no significant differences in the frequency of adverse events in two cohorts. There was no symptomatic heart failure, but 6 pts (10%) in cohort A and 5 pts (16%) in cohort B had > 10% asymptomatic decrease in LVEF. All patients were evaluable for pCR. Higher rates of pCR were achieved in the HER2pos/HRneg pts: 66% (n = 14) in cohort A, and 87% (n = 14) in cohort B. In group HER2pos/HRpos pts, the pCR rate was 48% (n = 18) vs 55% (n = 5) respectively. Conclusions: In HER2positive early breast cancer, a dual blockade (trastuzumab and pertuzumab) together with carboplatin and docetaxel neoadjuvant chemotherapy achieved higher rates of pCR ( 76%) compared with pts treated with trastuzumab, carboplatin and docetaxel (56%). However, a much higher percentage of pCR was observed in the group of patients with non-luminal cancers, who received a double blockade (87% vs 66%).