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Background Radiological complete response (CR-MRI) to neoadjuvant chemotherapy (NAC) by MRI predicts pathologic complete response (pCR) rates in pts with TNBC treated preoperatively with A/TX-based regimens and in some studies, it correlates with disease-free survival (DFS). The main aim of this study was to assess the relevance of the MRI response to primary chemotherapy associated with clinical stage and HER2 expression (Zero vs Low), in a cohort of 143 TNBC pts treated with A and TX +/- carboplatin (CP) in the NAC setting. Methods Retrospective study of pts treated with NAC for TNBC between January 2002 and June 2021, who underwent MRI to assess tumour response before NAC, after 4 cycles of anthracycline and cyclophosphamide (AC) and after TX. Survival analysis was based on the Kaplan-Meier and survival curves were compared using the log-rank test. A p value of less than 0.05 was considered as statistically significant. Results A total of 143 TNBC pts with a median age of 52 years; 7, 63 and 73 pts had stage I, II and III disease, respectively. The NAC regimen consisted in 117 pts 4 cycles of AC followed by TX and in 24 pts the same adding CP (in 21 pts with non-CR-MRI, 2 with CR-MRI and 1 without MRI after AC). PCR was observed in 41%. Of 30 pts with CR-MRI after AC, 83% obtain a pCR (p< 0.001), and of 52 pts with CR-MRI at the end of NAC, 70.7% obtain a pCR (p< 0,001) of which 90% had a CR-MRI after AC. Adding CP increased pCR by 6% (p=0.564). According HER2-zero vs low expression, the pCR was 38% and 47% respectively, with no significant differences. With a median follow-up of 60 months, 34% recurred and 16% died of TNBC. In pts with pCR, the DFS at 5 years (y) was 96% and 47% for pts without pCR (p< 0.001), with a DFS of 91% if CR-MRI at the end of NAC and 48% if non-CR-MRI (p< 0.001). In HER2-Zero tumours the DFS at 5 y was 64% vs 66% in HER-2 low. Interestingly, overall survival (OS) at 5 y was 72% in HER2-Zero and 84% in HER2-low (p=0.080). Conclusions Performing serial MRI in the course of NAC in TNBC may be a reliable indicator of pCR, adding platinum to TX in pts with CR-MRI may increase pCR rate. HER2-Zero expression in TNBC, seems to confer worse OS rates. Citation Format: Marina Sierra Boada, Luis Antonio Fernandez, Elsa Dalmau, Gemma Llort, Maria Marin, Pablo Andreu, Natalia Lopez, Carla Climent, Marta Rodriguez, Sandra Soriano, Miquel Angel Segui. Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy. [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 P4-07-40.

Neoadjuvant clinical trials with dual HER2 blockade with pertuzumab and trastuzumab plus chemotherapy demonstrated high rates of pathological complete response (pCR) in HER2-positive early breast cancer (BC). We investigated whether the benefit on pCR seen in clinical trials is confirmed in a real-world setting. Multicenter, retrospective study in patients with HER2-positive early BC receiving neoadjuvant treatment with pertuzumab and trastuzumab in routine clinical practice (n = 243). The primary endpoint was total pCR (tpCR) (ypT0/is ypN0). A total of 243 evaluable patients were included. Pertuzumab and trastuzumab were combined with anthracyclines and taxanes in 74.1% of patients, with single-agent taxane in 11.1% of patients and with platinum-based chemotherapy (CT) in 14.4% of patients. The tpCR rate was 66.4%:71% with anthracyclines and taxanes, 59.3% with single-agent taxane, and 48.6% with platinum-based combinations. The tpCR rate was higher among patients with hormone receptor (HR)-negative tumors (80.9%) vs HR-positive tumors (55.4%) (p

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.

Purpose Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non–small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. Patients and Methods Patients previously treated with one to two chemotherapy regimens (including one platinum-based regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results In all, 960 patients were randomly assigned, and baseline characteristics were balanced. Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone (hazard ratio [HR], 0.922; 95% CI, 0.797 to 1.067; one-sided stratified log-rank P = .1388). Median PFS was 3.6 months versus 2.0 months (HR, 0.807; 95% CI, 0.695 to 0.937; one-sided stratified log-rank P = .0023), and ORR was 10.6% versus 6.9% (two-sided stratified log-rank P = .0471), respectively. Treatment-related toxicities of grade 3 or higher, including rash/dermatitis, diarrhea, and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm. Conclusion In patients with refractory NSCLC, sunitinib plus erlotinib did not improve OS compared with erlotinib alone, but the combination was associated with a statistically significantly longer PFS and greater ORR. The incidence of grade 3 or higher toxicities was greater with combination therapy.

Background: In Europe, approximately 381,500 patients are diagnosed with non-small cell lung cancer (NSCLC) every year. The aim of this study is to analyse the changes in diagnosis, treatment and evolution during the last two decades, using data from a hospital registry. Material and Methods: Patients diagnosed with NSCLC at the Corporacio Sanitaria Parc Tauli-Sabadell (Catalonia, Spain) during the periods 1990-1997 (n=748) and 2003-2005 (n=311) were included. The hospital tumour registry was used for prospective data collection. Results: Our series shows a significant increase in women diagnosed with NSCLC (6% vs 10.3%; p 0.01) in the latter period; the incidence of adenocarcinomas increased by 20% (31% vs 51.1%), whereas that of squamous cell carcinomas fell (51.3% vs 32.5%; p

Background Docetaxel–cyclophosphamide (TC) has become a common regimen in moderate-high-risk early breast cancer (EBC), but the incidence of chemotherapy-induced nausea and vomiting (CINV) with this regimen is not well established. This trial investigates the effect of guideline-consistent prophylaxis on CINV related to TC regimen and explores the efficacy of aprepitant among resistant patients. Patients and Methods This prospective multicentre study enrolled 212 chemotherapy-naive EBC patients receiving T-75 mg/m 2 and C-600 mg/m 2 . Antiemetic therapy on the first cycle consisted of dexamethasone for 3 d plus 5-hydroxytryptamine (5-HT 3 ) antagonists on day 1, according to Multinational Association of Supportive Care in Cancer guidelines. The primary end-point was complete response (CR) (no emesis and no need of rescue treatment within the initial 120 h). Patients failing CR on cycle 1 entered in a single-arm study exploring the efficacy of aprepitant on the second cycle. Patients' diaries and Functional Living Index-Emesis (FLIE) questionnaires were collected in cycles 1 and 2. Results Among the 185 evaluable patients on cycle 1, 161 (87%, 95% confidence interval [CI]: 82.2–91.8) achieved a CR. Twenty-three patients received aprepitant on cycle 2, and 12 reached a CR (52.2%, 95% CI: 31.8–72.6). The absence of CR had a very substantial impact on quality of life on cycles 1 (FLIE before and after: 23.8–38.1, p = 0.0124) and 2 (18.3–42.9, p = 0.0059). Conclusions Guideline-consistent antiemetic prophylaxis for the TC regimen is associated with a low incidence of CINV. Aprepitant is effective as secondary prevention of CINV and should be considered as rescue therapy in patients treated with moderate emetogenic chemotherapy.

The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease. The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy. However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research. This review focuses on current and emerging treatments for HR+ metastatic breast cancer.

Haemolytic uraemic syndrome (HUS) is a rare thromboembolic complication observed in patients with cancer. It is characterised by the clinical triad of acute renal failure, microangiopathic haemolytic anaemia and thrombocytopaenia. It may be associated with a variety of aetiologies, including chemotherapeutic agents such as mitomycin, cisplatin, bleomycin, 5-fluorouracil and, most recently, gemcitabine. We report a 70-year-old patient treated with gemcitabine who developed haemolytic uraemic syndrome.

In clinical practice, it is possible to classify breast tumors according to estrogen receptor (ER), progesterone receptor (PgR), and HER2 overexpression: ER negative, PgR negative, and HER2 overexpressing; ER negative, PgR negative, and HER2 negative; ER positive, PgR positive, and HER2 negative; ER positive, PgR positive, and HER2 overexpressing; and the less frequent remaining 4 combinations. The aim of this study was to determine the percentage of pathologic complete response (pCR) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant or primary chemotherapy with anthracyclines and taxanes grouped according to ER, PgR, and HER2 status.Patients with LABC treated with primary chemotherapy including anthracyclines and taxanes were grouped according to ER, PgR, and HER2 status; pCR rates were analyzed using the chi(2) test; and correlations with a P value ofor = 0.05 were considered statistically significant.A total of 103 patients were treated. Only 100 patients were included for the analysis of pCR. Eighteen patients exhibited pCR. The pCR rate for each subgroup was as follows: 39.1% (9 of 23) had ER-negative, PgR-negative, and HER2-negative disease (P0.01); 35.7% (5 of 14) had ER-negative, PgR-negative, and HER2-overexpressing disease; 33.3% (3 of 9) had ER-positive, PgR-positive, and HER2-overexpressing disease; and 2.8% (1 of 36) had ER-positive, PgR-positive, and HER2-negative disease (P0.01).In patients with LABC, grouping breast tumors according to ER, PgR, and HER2 status can help predict pCR to primary chemotherapy.

Gastrointestinal stromal tumours (GIST) are mesenchymal tumours of the digestive tract originated in the interstitial cells of Cajal. They express the tyrosine kinase c-kit (CD117) activity receptor. Mutations in this receptor cause neoplastic development. Curative treatment continues to be radical resection of the tumour and is resistant to commonly employed chemotherapy regimens. Imatinib mesilate is a drug that inhibits c-kit activity expressed by GIST and its activity in these tumours has been demonstrated.Retrospective study of all cases of leiomyoma, leiomyosarcoma, schwannoma, and stromal or mesenchymal tumors from 1989 to July 2004. C-kit and CD34 proteins were detected at immunohistochemical study in addition to the usual markers for mesenchymal tumours.49 GISTs were diagnosed, 26 males and 23 females (mean age 64.1). Symptoms were digestive tract bleeding (n = 13), abdominal pain (n = 13), intestinal occlusion (n = 4) and others. The lesion was located in small bowel (n = 22), stomach (n = 19), rectum (n = 3), peritoneum (n = 2), esophagus (n = 1), omentum (n = 1), and retroperitoneum (n = 1). Forty-three of the 49 patients underwent surgery; radical resection was performed in 37 (75.5%) and palliative surgery in the other six (16.2%). Two of the patients that did not undergo surgery received chemotherapy. At the time of study, 28 (57.14%) patients remained alive, 23 (46.9%) of whom were disease- free and five (10.2%) were not. Nineteen (38.7%) patients died.The results of our series are similar to the others published. Before the year 2001, surgery was the only successful option for the GIST. Surgical resection continues being the best treatment to definitively cure this disease. Imatinib is used to treat not only resectable tumours, but even to allow the possibility to make a subsequent rescue surgery. On the other hand, Imatinib is used in the treatment of the metastatic disease.

e17015 Background: Vandetanib is a multikinase inhibitor (MKI) directed against VEGFR2-3, RET, RET/PTC and EGFR that has demonstrated significant efficacy in advanced MTC in a large phase III trial...

AimThe aim of the present study was to analyze the age of breast cancer patients managed with curative approach at the time of treatment with radiotherapy.BackgroundBreast cancer is the most frequent neoplasm in women. Little is known with regard to the age of patients at diagnosis, and some authors have suggested that breast cancer is now affecting women who are younger than before.Materials and methodsWe performed a descriptive study of our series of breast cancer patients from 1998 to 2011. The age of patients, city of residence, year of treatment and uni- or bilateral location were extracted from the administrative database of the Radiation Oncology Department. The demographical and reference populational data were extracted from the Catalan Institute of Statistics.Results3382 patients were obtained. The mean age was 57.79 years. No statistical differences were observed in the mean age during the period of study (p>0.05), nor in patients with bilateral neoplasias with regard to unilateral tumours (p>0.5). Patients aged less than 30, 40, 50 and 65 years were 0.3%, 6.3%, 27.0% and 69.1%, respectively. The proportion of patients aged less, equal or more than 40 and 50 years was not statistically different.ConclusionsBreast cancer patients treated with adjuvant radiotherapy after radical surgery have not experienced significant changes in their mean age at treatment. The subgroups of patients that remain out of the mammographic screening programmes were unchanged as well. The observed differences can be explained by demographical disparities and by a probable increase in the indications for adjuvant radiotherapy.