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Background: Talazoparib (TALA) is a highly potent PARP inhibitor that has demonstrated clinical benefit in the phase III EMBRACA trial for patients with germline BRCA1 or BRCA2-mutation and a locally advanced or metastatic HER2 negative (HER2-) breast cancer (BC). Methods: ViTAL is an ambispective, multi-center longitudinal, phase IV study that aims to ensure the effectiveness and safety of TALA in the real-world setting among patients with locally advanced or metastatic HER2- BC, with somatic or germline BRCA mutation (sBRCA or gBRCA). This study includes two cohorts: - Cohort 1: patients treated through the French Early Access Program from November 2018 to September 2019. Inclusion of patients with sBRCA mutation was allowed. - Cohort 2: patients treated according to the European Marketing Approval granted 21/09/2021. The primary endpoint is Time to Treatment Discontinuation (TTD) for TALA defined as Time between the date of first dose of TALA and the date of last dose or death. Results: We present the results of Cohort 1 in which includes 85 patients. Patients’ characteristics are as follows: median age 50 years; 46% triple negative BC and 54% ER+ BC; 47% BRCA1-mutated and 53% BRCA2-mutated; 94% gBRCA and 6% sBRCA; 95% ECOG PS 0 or 1; 31% premenopausal status; 40% de novo metastatic BC (mBC). Visceral, bones and central nervous system metastases were found in 61%, 54% and 11% of patients, respectively. No breast or ovarian cancer in first degree relative was found in 35 patients (41%). The median number of prior cytotoxic regimen was 2, 15% were chemo-naïve for mBC; 35% received prior platinum in the neoadjuvant, adjuvant or metastatic setting. For patients with ER+/HER2- mBC the median number of prior endocrine therapy was 2 and 74% of these patients received a CDK4/6 inhibitor prior to TALA. The median follow-up was 17.4 months [range 15.7-20.5]. Of 85 treated patients, 66 patients (78%) experienced permanent discontinuation of TALA due to progressive disease (88%), toxicity (8%), cancer-related death (3%), or other reasons (1.5%). The median TTD for TALA was 9.0 months [range 6.0-11.0] with 35% of patients still in under treatment at 12 months. At least one adverse event (AEs) was recorded in 71% of patients. Hematologic AEs (any grade) occurred in 44% of patients (anemia for 26%, thrombocytopenia for 9%, neutropenia for 8%). The most common non-hematologic AEs were alopecia (6%) and asthenia (5%). Related serious hematologic AEs occurred in 7 (8%) patients including 6 (7%) with anemia. Related serious non-hematologic AEs (vomiting, pyelonephritis) were seen in 2 patients (2%). AEs associated with temporary drug interruption, dose modification and permanent drug discontinuation occurred in 32 (38%), 16 (19%), and 5 (8%) patients respectively. After discontinuation of TALA, 83% of patients received a subsequent treatment with a TTD of 2.4 months [range 1.7-3.3]. The most common subsequent treatments were non-platinum chemotherapy (64%) and platinum therapy (24%). Conclusions: The TTD of 9 months is consistent with the outcomes and safety results of the EMBRACA study. ViTAL, the first real-word study with TALA confirms its interest in locally advanced or metastatic HER2- BC. Analysis of Cohort 2 will occur when data are mature. (Ref Litton JK, Rugo HR, Ellt J et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med. 2018; 379:753-763. Citation Format: Delphine Loirat, Marie Duboys de Labarre, Christine Essner, Ioana Hrab, Jean-Christophe Thery, Christelle Jouannaud, Cristian Villanueva, Perrine Vuagnat, Pauline Soibinet-Oudot, Anne Creisson, Audrey Mailliez, Jean-Loup Mouysset, Laura Salabert, Nadine Dohollou, Jean-David Fumet, Thibault De La Motte Rouge, Jean-Michel Vauthier, Maylis Decrop, Pascal Pujol. Phase IV study evaluating effectiveness and safety of talazoparib in patients with locally advanced or metastatic HER2 negative breast cancer and a BRCA1 or BRCA2 mutation (ViTAL) [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 P1-18-28.

INTRODUCTION: The management of cancer patients changed in the recent years with increased in the number of oral antineoplastic agents (OANA) prescriptions. Recent guidelines encouraged improvement of information and patient education, and the coordination between health care professionals to secure and optimize the management of these drugs. To cope with current recommendations, a multidisciplinary consultation (MDC) for initiation of OANA was initiated at François Baclesse comprehensive cancer center in Caen, France. OBJECTIVE: The aim of this study was to evaluate the benefit of the MDC before the initiation OANA in patients with metastatic breast cancer. MDC consisted of a medical oncologist, hospital pharmacist, and oncology nurse consultations. Primary endpoint was the rate of hospitalizations. Secondary endpoints were treatment discontinuation and of adverse events rate. MATERIALS AND METHODS: We conducted a retrospective single center study comparing patients receiving MDC to the population with a single medical visit. RESULTS: A total of 482 patients were included in this study between January 2017 and December 2019 (329 patients had only a consultation with a medical oncologist before initiation of OANA and 153 had the MDC). A statistically significant decrease in the rate of hospitalizations for toxicity was found in the group of patients with MDC 3.9% (n=6) vs 18.5% (n = 61) in the group without MDC (p < 0.001). A significant decrease in treatment interruption rate for toxicity was found in the group of patients with MDC 11% (n = 16) vs 26% (n=86) (p < 0.001). Adverse events rate was not statistically significant between the two groups CONCLUSION: A statistically significant decrease in hospitalizations and rate of treatment interruption for toxicity was observed after initiation of MDC in patients with a metastatic breast cancer treated with an OANA. This process should be generalized for a better security in the management of the OANA. Citation Format: Adeline Morel, Margaux Jacobs, Angelique Da Silva, Djelila Allouache, Ioana Hrab, Carine Segura, Maud Villemin, Clémence Boscher, Alison Johnson, Charlotte Ceintre, Rose-Marie Charles, François Lahaye, Justine Lequesne, Fabienne Divanon, Christelle Levy, Georges Emile. Benefit of multidisciplinary consultation at initiation of oral antineoplastic agents in metastatic breast cancer patients [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 P4-12-05.

Background: Talazoparib (TALA) is a highly potent, dual-mechanism PARP inhibitor that has demonstrated clinical benefit in EMBRACA Phase III trial for patients with germline BRCA1/2 (BRCA1/2)-mutated locally advanced or metastatic HER2- breast cancer. Objective: The aim of the study is to ensure the effectiveness and safety of TALA in the real-world setting among patients with locally advanced or metastatic HER2- breast cancer, with somatic or germline BRCA1/2 mutation. Methods: ViTAL is an ambispective, multicentric, longitudinal, phase IV study. It includes two ambispective cohorts: - Cohort 1: patients treated through the French Early Access Program and inclusion of patients with somatic BRCA1/2 mutation was allowed. - Cohort 2: patients treated according to the European Marketing Approval granted in 09/21/2021. The primary endpoint of the study is the Time to Treatment Discontinuation (TTD) which is defined as time between the date of first dose of TALA and the date of last dose or death. Results: From November 2018 to May 2021, 85 patients were included in Cohort 2, Patients’ characteristics are: - a median age of 49.0 years; - 65.8% ER+ BC/34.2% TNBC; - 42.1% mBRCA1/55.3 % mBRCA2/2,6% mBRCA1 and mBRCA2. - 85.7% ECOG PS 0 or 1; - 23.4% de novo mBC. - Visceral, bones and CNS metastases were found in 59.0%, 61.5% and 10.3% of patients respectively. - No breast or ovarian cancer family history at 1st degree was found in 39 patients (50.0%). - 38.5% were chemo-naïve; - 21.8% received prior platinum in (neo)adjuvant or metastatic setting, with a median of prior cytotoxic regimen of 1 - For patients with ER+/HER2- ABC the median number of prior endocrine therapy was 1 and 62.0% of these patients received a CDK4/6 inhibitor prior to TALA. - 8 patients (10.3%) had CNS metastases. Out of the 78 treated patients, 57 patients (73.0%) experienced a TALA permanent discontinuation for Progressive disease (80.7%), toxicity (12.3%), cancer-related death (1.8%), or other reasons (1.8%). The median TTD for TALA is 9.6 months [6.7;10.8] with 34.5% of patients still on treatment at 12 months. After discontinuation of TALA, 59.0% of patients received a subsequent treatment with a TTD of 3.9 months [2.1; 45]. The most common subsequent treatments were non-platinum chemotherapy (67.4%), platinum therapy (6.5%) and other (26.1%). The Clinical Benefit Rate assessed by the investigators is 87.6% (Complete Response for 14.1%, Partial Response for 56.3% and Stable Disease for 17.2%). The median duration of CNS metastases control was 10.2 months, and 25.0% of patients had a control of CNS metastases. At least one adverse events (AEs) was recorded in 67.9% of patients. Hematologic adverse events (AEs) (any grade) occurred in 55.1% (anemia 37.2%, thrombocytopenia 16.7%, neutropenia 15.4%). Most common non-hematologic AEs were Nausea (15.4%) and asthenia (15.4%). Related Serious Hematologic AEs occurred in 6 patients (7.7%) including 3 (3.8%) thrombocytopenia and 3 (3.8%) anemia. Related Serious Non-hematologic AEs (metrorrhagia) were seen in 1 patient (1.3%). AEs associated with temporary drug interruption, dose modification and permanent drug discontinuation occurred in 26 (33.3%), 22 (28.2%), and 7 (12.3%) patients respectively. The mOS is not mature for this analysis. Conclusions: ViTAL is the largest study that reports real-word data with TALA. Outcomes and safety in Cohort 2 (patients treated with TALA according to the European Marketing Approval), are consistent with the results of EMBRACA study and with the Cohort 1. (Litton et al. NEJM 2018) Citation Format: Delphine Loirat, Marie Duboys de la barre, Cristian Villanueva, Audrey Mailliez, Nicolas Isambert, Lionel Moreau, Emmanuelle Jacquet, Dominique Spaëth, Anne Creisson, Christelle Jouannaud, Eric Legouffe, Miguel delbado, Laura Deiana, Pauline Soibinet, Ioana Hrab, Thomas grellety, Nadine Dohollou, Raffaele Longo, Jean-Christophe Thery, Jean-david Fumet, Sellam Zineb, Pascal Pujol, thibault DE LA MOTTE ROUGE. Phase IV multicenter study evaluating RWE and the safety of talazoparib in patients with locally advanced or metastatic negative HER2 breast cancer and a BRCA1/2 mutation (ViTAL) - Cohort 2: patients treated according to the EMA [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 P4-01-04.

Background: Talazoparib (TALA) is a highly potent, dual-mechanism PARP inhibitor that has demonstrated clinical benefit in EMBRACA Phase III trial for patients with germline BRCA1/2 mutated locally advanced or metastatic HER2- breast cancer. Objective: The aim of the study is to ensure the effectiveness and safety of TALA in real-life setting among patients with locally advanced or metastatic HER2- breast cancer, with somatic or germline BRCA1/2 mutation. Methods: ViTAL is an ambispective, multicentric, longitudinal, phase IV study. It includes two ambispective cohorts: - Cohort 1: patients treated through the French Early Access Program and inclusion of patients with somatic BRCA1/2 mutation was allowed. - Cohort 2: patients treated according to the European Marketing Approval granted in 09/21/2021. Here we present the results of the primary and some secondary endpoints for cohort 1. Results: From November 2018 to May 2021, 86 patients were included in Cohort 1, with updated results after a median follow-up of 17.3 months (11.2 - 24.4). Patients’ characteristics are 53.5% of ER+ BC/46.5% of TNBC (refer to the table). The median Time to Treatment Discontinuation (mTTD) was 9.0 months [range 6.0; 11.5] with 37.7% of patients still on treatment at 12 months. Subgroup analysis shows similar mTTD according HR status, germline vs somatic mutation and prior platinum exposure (refer to the table). The Clinical Benefit Rate assessed by the investigators is 82.4% (Complete Response for 25.7%, Partial response R for 32.4% and stable disease for 24.3%). The median of duration of CNS metastases control was 6.6 months, and 80.0% of patients had control of CNS metastases during TALA. Out of the 85 treated patients, 69 patients (80,2%) experienced a TALA permanent discontinuation for progressive disease (84.1%), toxicity (10.1%), cancer-related death (1.4%), or other reasons (1.4%). After discontinuation of TALA, 65.1% of patients received a subsequent treatment with a TTD of 2.3 months [1.7; 2.7]. The most common subsequent treatments were non-platinum chemotherapy (64.3%), platinum chemotherapy (19.6%) and others (19.1%). At least one adverse events (AEs) was recorded in 74.4% of patients. Hematologic AEs (any grade) occurred in 48.8% (anemia 27.9%, thrombocytopenia 12.8%, neutropenia 10.5%). Most common non-hematologic AEs were alopecia (8.1%) and asthenia (7.0%). Related Serious Hematologic AEs occurred in 10 patients (11.6%) including 7 (8.1%) Anemia. Related Serious Non-hematologic AEs (vomiting, pyelonephritis and ascitis) were seen in 3 patients (3.6%). AEs associated with temporary drug interruption, dose modification and permanent drug discontinuation occurred in 36 (41.9%), 24 (27.9%), and 7 (10.1%) patients respectively. The mOS is expected to be reached at the time of the congress, with 51.9% of patients still alive at 24 months. Conclusions: ViTAL is the largest study that reports real-word data with TALA. Outcomes and safety in Cohort 1 are consistent with the results of EMBRACA study and give additional data on subgroups of interest (ie patients previously treated with carboplatin, presence of CNS). (Litton et al. NEJM 2018) mTTD on subgroups of interest Patients’ characteristics Citation Format: Delphine Loirat, Marie Duboys de la barre, Jean-Christophe Thery, Ioana Hrab, Christelle Jouannaud, Jean-Loup Mouysset, Laura Salabert, Pauline Soibinet, Audrey Mailliez, Romain Valery, Anne Creisson, Cristian Villanueva, Nadine Dohollou, Jean-david Fumet, Thomas grellety, Nathalie Perez-staub, Emma Lachaier, Aurore Iltis-roux, Miguel delbado, Abeer Najem, Romuald Le Scodan, Elsa Curtit, kais aldabbagh, Pascal Pujol, thibault DE LA MOTTE ROUGE. Phase IV study evaluating talazoparib in patients with locally advanced or metastatic negative HER2 breast cancer and a somatic or germline BRCA1/2 mutation (ViTAL) – Analysis of cohort 1 according to hormonal receptor status [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 P4-01-20.

Background/aim Currently, there is no recommendation for the treatment of breast cancer (BC) with bone-marrow cell infiltration (BMI). We evaluated the efficacy and safety of weekly-paclitaxel in this population. Patients and methods This retrospective study included all BC patients with BMI receiving weekly-paclitaxel between January 2014 and May 2018. Overall-survival (OS) was the primary endpoint. Secondary endpoints were progression-free-survival (PFS) and safety. Results BMI was diagnosed in 26 patients. This infiltration was suggested by peripheral blood smear in 73% of cases. All patients had anemia, and 77% had thrombocytopenia. OS and PFS were 7.2 months [95% confidence interval (CI)=2.6-20.7] and 3.3 months (95%CI=1.6-7.2), respectively. Good performance-status, absence of thrombocytopenia and presence of less than 5% of circulating erythroblasts at BMI diagnosis, were associated with better survival. One patient presented grade 5 febrile neutropenia but no episodes of bleeding were reported. Conclusion Weekly-paclitaxel is an effective therapeutic option with limited toxicity for BC with BMI.

Cyclin-dependent-kinase 4–6 inhibitors (CDK4/6i) have improved the management of hormone receptor (HR)(+)/human epidermal growth factor receptor (HER)2(−) metastatic breast cancer (mBC). Currently, there are no valid prognostic factors for response to CDK4/6i. Baseline lymphopenia is reported as a prognostic factor in several types of cancer. The present retrospective study aimed to evaluate the effect of baseline absolute lymphocyte count (ALC) on response to palbociclib. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints were overall survival (OS), best response and safety. A total of 114 patients treated for mBC between 2016 and 2019 were included. Median baseline ALC was 1.4 g/l (range, 0.2-4.3 g/l). A total of 65 (57%) and 49 (43%) patients had baseline ALC values of

Background Brain metastases often occur in cancer evolution. They are not only responsible for death but also for disorders affecting the quality of life and the cognitive functions. Management of brain metastases usually consists in multi-modality treatments, including neurosurgery, whole brain radiotherapy (WBRT), and more recently radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT), systemic treatment (chemotherapy or targeted therapy), combined or not with corticosteroids. Almost 20% of brain metastases can present recent (within 15 days) bleeding signs on neuro-imagery. In these conditions, WBRT is the usual treatment. Yet, patients may benefit from a more aggressive strategy with SRT or FSRT. However, these options were suspected to possibly major the risk of brain haemorrhage, although no scientifically proven. Radiation oncologists therefore usually remain reluctant to deliver SRS/FSRT for bleeding brain metastases. It is therefore challenging to establish a standard of care for the treatment of bleeding brain metastases. We propose a phase II trial to simultaneously assess safety and efficacy of FSRT to manage brain metastases with hemorrhagic signal. Methods The STEREO-HBM study is a multicenter two-step non-randomised phase II trial addressing patients with at least one bleeding brain metastasis out of a maximum of 3 brain metastases. Each brain metastasis will be treated with 30 Gy in 3 fractions for 1 week. The main endpoint is based on both safety and efficacy endpoints as proposed by Bryant and Day’s design. Safety endpoint is defined as the rate of bleeding complications 4 months post-FSRT while efficacy endpoint is defined as the 6-month local control rate. Multi-modal MRI will be used to assess intra-tumoral hemorrhagic events before and after treatment. Patients’ quality of life will also be assessed. Discussion Management of bleeding brain metastases is still debated and poorly explored in clinical trials. There is sparse and weak data on the signification of pretreatment intra-tumour haemorrhagic signs or on the risk of brain bleeding complications after FSRT. We expect this first prospective phase 2 trial in this particular setting will allow to clarify the place of FSRT to optimally manage bleeding brain metastases. Trial registration NCT 03696680, registered October, 4, 2018. Protocol version Version 2.1 dated from 2018/11/09.

Chemotherapy-induced nausea and vomiting (CINV) still remain frequent. The procedure for announcing the diagnosis (PAD) was an emblematic measure of the first French Plan Cancer aiming at providing patients with time to listen, information after cancer diagnosis, and discussion on treatments and their side effects. We aimed at assessing the risk factors of CINV, focusing on patients’ satisfaction with the PAD. This prospective multicentre study assessed the frequency and intensity of CINV among chemonaive patients during the first cycle of treatment. CINV was defined by ≥1 emetic episode or reported nausea intensity ≥3 on a 0–10 scale. Multivariate analysis was used to identify factors related to global CINV onset including satisfaction with the PAD (satisfaction score ≥the median on a 0–10 scale). Data from 291 patients (women, 85.2 %; mean age, 57 years) were analyzed. Most patients (69.4 %) received highly emetogenic chemotherapy regimens and 77.7 % received antiemetic drugs consistent with international guidelines. Acute, delayed and overall CINV were experienced by 40.4, 34.8 and 52.4 % of patients, respectively. Sixty-seven per cent of patients were satisfied with the PAD. No relation was noted between PAD satisfaction and CINV onset. The nausea and vomiting dimension of the QLQ-C30 questionnaire before chemotherapy (OR 3.62), motion sickness history (OR 2.73), highly emetogenic CT (OR 2.73), anxiety (OR 1.99) and younger age (OR 1.96) were independent predictive factors. Although patients were mostly satisfied with the PAD, half of them experienced CINV. A state of anxiety could be identified during the PAD to be managed.

Background Brain metastases (BMs) are associated with a poor prognosis. Standard treatment comprises whole-brain radiation therapy (WBRT). As neo-angiogenesis is crucial in BM growth, combining angiogenesis inhibitors such as bevacizumab with radiotherapy is of interest. We aimed to identify the optimal regimen of bevacizumab combined with WBRT for BM for phase II evaluation and provide preliminary efficacy data. Patients and methods In this multicentre single-arm phase I study with a 3 + 3 dose-escalation design, patients with unresectable BM from solid tumours received three cycles of bevacizumab at escalating doses [5, 10 and 15 mg/kg every 2 weeks at dose levels (DL) 0, 1 and 2, respectively] and WBRT (30 Gy/15 fractions/3 weeks) administered from day 15. DL3 consisted of bevacizumab 15 mg/kg with WBRT from day 15 in 30 Gy/10 fractions/2 weeks. Safety was evaluated using NCI-CTCAE version 3. BM response (RECIST 1.1) was assessed by magnetic resonance imaging at 6 weeks and 3 months after WBRT. Results Nineteen patients were treated, of whom 13 had breast cancer. There were no DLTs. Grade 1–2 in-field and out-field toxicities occurred for five and nine patients across all DLs, respectively, including three and six patients (including one patient with both, so eight patients overall) of nine patients in DL3. One patient experienced BM progression during treatment (DL0). At the 3-month post-treatment assessment, 10 patients showed a BM response: one of three treated at DL0, one of three at DL1, two of three at DL2 and six of seven at DL3, including one complete response. BM progression occurred in five patients, resulting in two deaths. The remaining patient died from extracranial disease progression. Conclusion Bevacizumab combined with WBRT appears to be a tolerable treatment of BM. DL3 warrants further efficacy evaluation based on the favourable safety/efficacy balance. Clinical trials.gov Identifier NCT01332929.

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Aim: The announcement device was an emblematic measure of the first French Plan Cancer aiming at enabling patients to have a listening and information time after diagnosis announcement and treatment proposition: the different aspects of the treatments including side effects are discussed during these specific clinics. This procedure includes a medical and paramedical consultation. Nausea and vomiting (CINV) are still one of the most common side effects of the chemotherapy (CT) despite of known risk factors and efficient supportive treatments. Hypothesizing patients with good information on CINV and preventive supportive treatments may have less CINV, our study aimed to assess the relation between the patient's satisfaction of information delivered during the diagnosis announcement procedure and the incidence of CINV after the first cycle of chemotherapy. Methods: This prospective multicentric study assessed the frequency and intensity of CINV among patients naive of CT after the first cycle of treatment, using the MASCC Antiemesis Tool (MAT). CINV were defined by≥1 emetic episode or reported nausea intensity≥3 on a 0-10 scale. Multivariate analysis was used to identify various factors related to overall CINV onset, including satisfaction defined as a satisfaction score equal or above median on a 0-10 scale for≥1 announcement consultation. Results: Data from 291 patients (women: 85.2%; mean age: 57 years) from 4 centers were analyzed. Median satisfaction score were 9 and 10 for medical/paramedical consultations (1st quartile: 8 and 9, respectively): 67% of patients were satisfied of announcement device. 40.4% of patients reported acute CINV, 34.8% delayed CINV and 52.4% overall CINV. Four independent predictive factors of CINV were found: motion sickness history (OR 2.73), highly emetogenic CT (OR 2.12), anxiety (OR 2.09) and age under 57 (OR 1.99). No relation was noted between announcement consultation satisfaction and risk of CINV. Conclusions: The announcement consultation satisfaction was not linked to lower CINV frequency. In fact, even "unsatisfied" patients gave a high score, not allowing to clearly identify the impact of satisfaction on CINV. Disclosure: All authors have declared no conflicts of interest.