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LBA1003 Background: PAL was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved for ER+/HER2– ABC based on the randomized, phase 2 PALOMA-1 study. PALOMA-2 is a randomized, double-blind, phase 3 trial in first-line ER+/HER2– ABC that confirmed a clinically and statistically significant improvement in progression-free survival (PFS) with PAL+LET versus PBO+LET (median PFS, 27.6 vs 14.5 months; hazard ratio, 0.56 [95% CI, 0.46–0.69]; P12 months, median OS (95% CI) was 66.3 months (52.1–79.7) in the PAL+LET arm (n=179) and 47.4 months (37.7–57.0) in the PBO+LET arm (n=93); hazard ratio, 0.728 (95% CI, 0.528-1.005). No new safety findings were observed. Conclusions: PALOMA-2 met its primary endpoint of improving PFS but not the secondary endpoint of OS. Pts receiving PAL+LET had numerically longer OS compared to PBO+LET, but the results were not statistically significant. Funding: Pfizer Inc (NCT01740427) Clinical trial information: NCT01740427.

e24019 Background: 11% of Ireland’s population is above the age of 65. This is projected to double to 1.4 million by 2040 corresponding to doubling of cancer cases. Clinical trials often exclude patients (pts) ≥70; therefore, it can be challenging to apply evidence based treatment (tx) to this population. Data from the National Cancer Registry of Ireland suggests under tx of older patients (pts). Comprehensive Geriatric assessment (CGA) is recommended by the National Comprehensive Cancer Network (NCCN) and the International Society of Geriatric Oncology (SIOG). In practice, CGA is limited by time constraints, lack of resources and expert interpretation. Geriatric screening tools can help identify frail pts who are most likely to benefit from CGA. The primary objective of this pilot study was to establish the prevalence of frailty (assessed by G8), presence of cognitive impairment (assessed by Mini-Cog), and risk of chemo-toxicity (assessed by Chemo-Toxicity Calculator) among pts ≥ 65 years (yrs) starting systemic anti-cancer tx. Methods: Pts ≥65yrs starting new systemic anticancer tx were identified between 1st of December 2020 to 31ST of September 2021 in St. Vincent’s University Hospital. Verbal consent was obtained. Printed versions of the G8 screening tool and Mini-Cog were used. CARG chemo-toxicity score was conducted online ( www.mycarg.org/tools ). .The assessment was conducted by consultants, specialist registrars and registrars. Data including pts’ age, type of malignancy, stage of cancer, and planned treatment were recorded. Analysis was conducted by SPSS statistical software, V.25(SPSS Institute, IBM Corp., 2017). Results: We identified 56 pts ≥65 years.27 (48.1%) were females and 29 (50.8%) were males. The majority of treated pts, N = 33 (58.1%) had metastatic cancer. The median G8 score was 12 (IQR 9.6-14). 83.9% of pts had a G8 score ≤14. Mini-Cog was found to be positive in 11 pts (19.6%). The median CARG score was 7 (IQR 6-11) and the median risk of toxicity 51% (IQR 44-78%). Of these, 44 (78.2%) received chemotherapy and 12 pts (21.4%) received non-chemotherapy systemic tx. In multi-variate analyses, age, type of cancer, planned treatment, and stage of disease did not impact G8, Min-cog, and CARG scores. Conclusions: In this single center study of elderly pts, more than 80% of pts had a positive G8 score representing a need for formal CGA assessment. The risk of toxicity was substantial with almost 50% risk of grade ≥ 3 toxicity in this cohort. Chronological age was not found to negatively impact patient’s frailty, cognition, or risk of toxicity. Interpretation of this pilot study is limited by small sample size, possible inter-operator variability, and lack of self-reported assessment.

502 Background: The 70-gene MammaPrint (MP) assay predicts risk of distant recurrence (DR) in hormone-receptor positive early-stage breast cancer and classifies cancers as Low Risk or High Risk. NSABP B-42 evaluated ELT in patients (pts) who had completed 5 yrs of adjuvant endocrine therapy (tx). The primary objective was to determine the utility of MP to identify pts enrolled in NSABP B-42 who are likely to benefit from ELT. Methods: A total of 1,866 pts from B-42 had available MP results. Primary endpoint is DR. Secondary endpoints are disease-free survival (DFS) and breast cancer-free interval (BCFI). For the primary analysis, pts were classified as High Risk (MP-H) (MP score ≤0.000) or Low Risk (MP-L) (MP score > 0.000). Exploratory analyses were performed for MP-L subcategories: MP Ultralow Risk (MP-UL) (MP score > 0.355) and MP-L but not MP-UL (MP-LNUL) (MP score > 0.000, ≤0.355). Likelihood ratio test based on stratified Cox proportional hazards (PH) model was used for treatment by risk group interaction. Stratified log-rank test was used to compare treatment groups. Hazard ratios and 95% CI were computed based on the stratified Cox PH model. Results: Among 1,866 pts, 706 (38%) were MP-H and 1,160 (62%) were MP-L. Of the MP-L, 252 (22%) were MP-UL. There were no significant differences in the distribution of patient and tumor characteristics between the MP group and the rest of the B-42 cohort, except for HER2 status. ELT effect was more pronounced in the MP cohort than in the overall B-42 population. For DR, there was statistically significant ELT benefit in MP-L (HR = 0.43, 95% CI 0.25-0.74, p = 0.002), but not MP-H (HR = 0.65, 0.34-1.24, p = 0.19) (interaction p = 0.38). For DFS, there was statistically significant ELT benefit in MP-L, but not MP-H (interaction p = 0.015). Similar findings were observed for BCFI (interaction p = 0.006). Within subcategories of MP-L, there was statistically significant ELT benefit in MP-LNUL, but not in MP-UL for all three endpoints, however the power in MP-UL was limited due to low number of pts (Table). Clinical trial information: 00382070. Conclusions: Statistically significant ELT benefit was observed for MP-L, but not MP-H. The treatment by risk group interaction was not statistically significant for DR, but it was for DFS and BCFI. The benefit appears to be stronger in MP-LNUL than in MP-UL. NCT: 00382070. Support: U10CA180868, -180822, U24CA196067; Novartis; Agendia.[Table: see text]

501 Background: The BCI HOXB13/IL17BR ratio (BCI-H/I) has been shown to predict endocrine tx (ET) and extended ET (EET) benefit. We examined the effect of BCI-H/I for EET benefit prediction in NSABP B-42, evaluating extended letrozole tx (ELT) in HR+ breast cancer patients (pts) who completed 5 yrs of ET. Methods: All pts with available primary tumor tissue were eligible. Primary endpoint was recurrence-free interval (RFI). Secondary endpoints were distant recurrence (DR), breast cancer-free interval (BCFI), and disease-free survival (DFS). Stratified Cox proportional hazards model was used. Due to a non-proportional effect of ELT on DR, time-dependent secondary analyses (≤4y, >4y) were performed. Likelihood ratio test evaluated treatment by BCI-H/I interaction. Results: In 2,179 pts analyzed (60% N0; 62% AI only; 80% HER2-), 45% were BCI-H/I-High and 55% BCI-H/I-Low. ELT showed an absolute 10y benefit of 1.6% for RFI (HR=0.77, 95% CI 0.57-1.05, p=0.10) (BCI-H/I-Low: 1.1% [HR=0.69, 0.43-1.11, p=0.13]; BCI-H/I-High: 2.4% [HR=0.83, 0.55-1.26, p=0.38]; interaction p=0.55). There was no statistically significant ELT by BCI-H/I interaction for BCFI (BCI-H/I-Low: HR=0.53, 0.36-0.78, p=0.001; BCI-H/I-High: HR=0.85, 0.60-1.21, p=0.36; interaction p=0.07) or for DFS (BCI-H/I-Low: HR=0.75, 0.58-0.95, p=0.017; BCI-H/I-High: HR=0.81, 0.64-1.04, p=0.09; interaction p=0.62). Before 4y, there was no statistically significant ELT benefit on DR in either BCI-H/I group. After 4y, BCI-H/I-High pts had statistically significant ELT benefit on DR (HR: 0.29, 0.12-0.69, p=0.003), while BCI-H/I-Low pts were less likely to benefit (HR: 0.68, 0.33-1.39, p=0.28) (interaction p=0.14). Conclusions: BCI-H/I prediction of ELT benefit on RFI was not confirmed. In time-dependent DR analyses, BCI-H/I-High pts had statistically significant benefit from ELT after 4y, while BCI-H/I-Low pts did not. Observed ELT benefit on BCFI in BCI-H/I-Low pts was primarily driven by second primary breast cancers. Additional follow-up is needed to further characterize BCI-H/I predictive ability in this study. Support: U10CA180868, -180822, U24CA196067; Novartis; Biotheranostics. Clinical trial information: NCT00382070. [Table: see text]

510 Background: Trastuzumab (T) increases the incidence of cardiac events (CEs) in patients (pts) with early breast cancer (BC). Dual blockade with P+T improves BC outcomes and is the standard of care for high-risk HER2-positive BC pts following the phase 3 APHINITY trial that evaluated the addition of P or placebo (Pla) to T and chemotherapy (CT). We analyzed the cardiac safety of P+T in APHINITY. Methods: APHINITY eligibility required a left ventricular ejection fraction (LVEF) ≥55% at study entry. LVEF assessment was performed every 3 months (mos) during treatment, every 6 mos up to month 36, and yearly thereafter. Primary CE was defined as heart failure (HF) class III/IV and a significant decrease in LVEF of at least 10 percentage points from baseline and to

540 Background: Treatment of hormone receptor positive (HR+) ESBC is evolving. The use of chemotherapy (CT) is declining with use of the 21-gene RS assay. This validated tool predicts the likelihood of adjuvant CT benefit in HR+ ESBC. Results from the TAILOR-x study suggest up to 70% of HR+ node negative ESBC patients (pts) may avoid CT with RS ≤25. Our objectives were to assess the clinical and economic impact of RS testing on treatment decisions using real-world data. Methods: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ node negative ESBC pts who had RS testing in Ireland. A survey of Irish breast medical oncologists provided the assumption for the decision impact analysis that grade (G) 1 pts would not receive CT pre RS testing and G2/3 pts would receive CT. Using TAILOR-x results, pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Data was collected via electronic patient records. Descriptive statistics were used. Cost data was obtained via the National Healthcare Pricing Regulatory Authority. The economic analysis was adjusted for changing treatment and assay costs over the study period. Results: 963pts were identified. Mean age 56 years. Mean tumour size 1.87cm. 114 (11.8%), 636(66%), 211(22%), 2(0.2%) pts had G1, G2, G3 and unknown G respectively (resp). 797pts (82.8%) had low RS, 159 (16.5%) had high RS, and 7pts(0.7%) unknown RS. 251pts(26%) were aged < 51 at diagnosis. Of these, 45(17.9%), 145(57.8%), 58(23%), 3(1.2) had G1, G2, G3 and unknown G resp. 208pts(82.9%) had RS ≤ 25, 39pts(15.5%) had RS > 25 and 4pts(1.6%) unknown RS. In the RS ≤ 25 group, 111pts(44%) had RS 0-15, 59(23.5%) had RS16-20, and 38(15.1%) had RS21-25. Post RS testing 595pts(61.8%) had a change in CT decision; 586 changed to hormone therapy (HT) alone, and 9 from HT to CT. In total, 227pts(23.5%) received CT, and 3pts(0.3%) declined. Of pts treated with CT; 9(4%) had RS 0-15, 89(39.2%) had RS16-25, 129(56.8%) had RS > 25. The most common CT regimen was docetaxel and cyclophosphamide(TC), administered to 121pts(53%). RS assay use achieved a 69% change in treatment decision among G2/3 pts and a net 61% reduction in CT use. This resulted in savings of over €4 million in treatment costs. Deducting the assay cost, net savings of over one million euro was achieved. Conclusions: Ireland was the first public healthcare system to approve reimbursement for RS testing. Over the 8 year period of the study, a net 61% reduction in CT use in Irish pts with HR+ ESBC was achieved with conservative net savings of over €1,000,000.

1036Background: PI3K pathway activation is implicated in resistance to trastuzumab (T) therapy in breast cancer (BC). Copanlisib (C) is a pan-class I PI3K inhibitor with particular activity against...

594Background: Inflammation plays an important role in cancer development and proliferation.Host systemic markers of inflammation including the neutrophil-to-lymphocyte ratio (NLR) have been associ...

e12522Background: Taxane-containing Adj is an accepted life-prolonging component of modern multi-modal ESB therapy. One of the most distressing complications of Adj is alopecia. While patients (pts...

1039 Background: Hormone tx (HT) is the primary 1L tx for ER+ ABC. In the PALOMA-2 study (NCT01740427), PAL+L as 1L ABC tx prolonged progression-free survival (PFS; hazard ratio [HR] 0.58; P12 mo (40%) than ≤12 mo (22%). Median PFS (mPFS) was improved in all subgroups by adding PAL to L (Table). Adverse events were consistent across subgroups, as described for the full study population. Conclusions: PAL+L improved mPFS vs P+L with manageable toxicity across all subgroups including those with visceral disease. PAL+L provides a 1L option that should be considered for all pts with ER+/HER2- ABC. Sponsor: Pfizer Clinical trial information: NCT01740427. [Table: see text]

587Background: ‘TCHL’ an ICORG phase-II neo-adjuvant study in HER2+ve Breast cancer (BC) assessed the impact of TCH (Docetaxel, Carboplatin, Trastuzumab) versus TCHL (Docetaxel, Carboplatin, Trastu...

e18261Background: Clinical trials are an important tool in improving health outcomes in oncology patients. They also allow access to drugs that may otherwise be unavailable to patients. Increasingl...

591Background: TCGA analysis revealed that somatic EGFR, ERBB2, ERBB3 and ERBB4 mutations (ERBB family mutations) occur alone or co-occur with somatic PIK3CA mutations in 19% of HER2-positive breas...

e11586 Background: Oncotype RS is used to assess recurrence risk and predict chemotherapy benefit for hormone positive, node negative, early stage breast cancer. There is a predicted recurrence rat...

e20656 Background: Alopecia induced by chemotherapy is a distressing side effect. It can have negative effects on patients' self-esteem, body image and adversely influence choice of chemotherapeuti...

e17561 Background: Doubling time in non-SCLC tumors has been well studied, but this is less so in SCLC. We aim to study in vivo doubling time in SCLC using modern imaging techniques. Methods: Patients (pts) with SCLC with both diagnostic computed tomography (CT) and subsequent staging Positron Emission Tomography (PET)/CT were identified from institutional database. Primary lesion and nodal disease on the initial CT scan and on the CT component of PET/CT scan was measured. Diameter Doubling Time (D-DT) = [(dt)*log 2] / [3(log D2 – log D1)], where dt was time interval between scans, D2 and D1 are diameters of lesion on second and first scan respectively. Volume Doubling Time (V-DT) = [(dt)*log 2] / (log V2 – log V1), where V2 and V1 are volume of 2nd and 1st CT. Results: 18 eligible pts were identified. 61% were males, median age 63. Primary lesion was assessable in 14 pts and nodal disease in 17. Mean interval between scans was 19.7 days (range: 6 – 67). Mean diameter of primary lesion on 1st and 2nd scans: 4.17 cm +/- 2.11 and 4.63 cm +/- 2.26. Mean diameter of lymph nodes on 1st and 2nd scans: 4.24 cm +/- 1.72 and 4.78 cm +/- 1.81. Mean volume of primary lesion on 1st and 2nd scans: 35.56 cm3 (=/- 43.34) and 45.52 cm3 (+/- 55.66). Mean volume of nodal disease on 1st and 2nd scans: 32.77 cm3 (+/- 44.52) and 44.16 cm3 (+/- 55.06). For primary tumor, mean D-DT was 70.0 days +/- 16.4, with mean V-DT 60.5 days +/- 11.8, p=.64. There is a significant correlation between D-DT and V-DT with Pearson rho of 0.7691 (p=0.0013). For nodal disease, mean D-DT = 51.1 days +/- 15.1 and mean V-DT 42.2 days +/- 9.3, p= .62, with correlation between D-DT and V-DT, Pearson rho of 0.7609, p=.0004. There was higher doubling time in extensive stage (ES) SCLC primary tumors compared with limited stage (LS), with mean D-DT 24.0 days vs 97.6 days, p=.046. When all lesions analyzed collectively, mean D-DT = 59.6 days, 95% CI 37.1 – 82.2 and mean V-DT = 50.5 days, 95% CI 35.3 – 65.7. Conclusions: Our data demonstrate more rapid doubling time of SCLC compared to historical data. The differential in growth between LS and ES points to a biologic dichotomy. This has a significant impact in the timely management of SCLC, and potential avenues for therapeutic development.

e11065 Background: In randomised trials IRx consisting of chemotherapy (cRx) + H produced pathological complete responses (pCR, defined variously as absence of invasive cancer, or, absence of invasive and in-situ cancer) in 29-40% of pts with HER2+ BC. Most of the regimens which have been studied include an anthracycline (A), raising concerns about cardiac toxicity from H +A. Our unit adopted the non-A based TCH regimen which was developed by the BCIRG, as our standard for both IRx and adjuvant Rx of HER+BC in 2006, following the presentation of the data from the BCIRG 006 trial, in which TCH produced similar levels of activity to a more aggressive A+H containing regimen, but with substantially less cardiac toxicity. In preparation for a random assignment trial in which TCH will be compared to TC+/- Lapatinib (L) +/- H we studied the efficacy of the TCH regimen in producing pCR. Methods: We reviewed the records of all patients that received IRx TCH. The TCH regimen consisted of T 75mg/m2, C AUC 6 and H 6m...