Serafin Morales Murillo (Alpicat, Spain)
Hospital Arnau de Vilanova - LleidaAuthor Of 2 Presentations
95P - PAM50 HER2-enriched phenotype as a predictor of early response to neoadjuvant lapatinib plus trastuzumab HER2-positive breast cancer: Survival results of the SOLTI-PAMELA study (ID 107)
- Tomas Pascual (Barcelona, Spain)
- Begona Bermejo De Las Heras (Valencia, Spain)
- Noelia Martinez (Madrid, Spain)
- Ana Mafalda Antunes De Melo e Oliveira (Barcelona, Spain)
- Sonia Pernas Simon (L'Hospitalet de Llobregat, Spain)
- Rafael Lopez Lopez (Santiago de Compostela, Spain)
- Isabel Ruiz Cabrero (Tarragona, Spain)
- Jesús D. Alarcón (Palma de Mallorca, Spain)
- Eduardo Martinez De Dueñas (Castellon de la Plana, Spain)
- Diego Malon Gimenez (Fuenlabrada, Spain)
- Maria Gonzalez Cao (Barcelona, Spain)
- Luis M. Manso Sanchez (Madrid, Spain)
- Serafin Morales Murillo (Alpicat, Spain)
- Helena Lopez de Ceballos (Caceres, Spain)
- Javier Cortes (Madrid and Barcelona, Spain)
- Antonio Llombart Cussac (Valencia, Spain)
- Aleix Prat (Barcelona, Spain)
Abstract
Background
The PAMELA trial tested the hypothesis that patients (pts) with the HER2-enriched (HER2-E) subtype benefit the most from dual HER2 blockade. Here, we evaluated the survival outcomes of this trial.
Methods
PAMELA is a non-randomized, open-label, multicentric, prospective translational research study in stage I-IIIA HER2+ breast cancer designed to evaluate the ability of the PAM50 intrinsic subtypes to predict pCR in the breast (pCRB; in situ allowed) following 18 weeks of neoadjuvant lapatinib and trastuzumab. Patients with HR+ disease received letrozole (if postmenopausal) or tamoxifen (if pre-menopausal). The primary objective was to compare the pCRB rates of the HER2-E versus the non-HER2-E subtypes in the intent-to-treat population. Exploratory endpoints included disease-free survival (DFS) and distant disease-free survival (DDFS) measured from the date of surgery.
Results
139 (92%) of 151 included pts from PAMELA had follow-up information after surgery. 127 (91.4%) pts received adjuvant chemotherapy (CT), 69 (49.6%) pts with anthracycline-based CT. Median follow-up was 76.7 months [1.2-91.6]. 13 (9.4%) relapse events have occurred (9 distant metastatic events, 1 contralateral recurrence, 2 invasive locoregional relapses [ILR] and 1 in situ recurrence). 6 year DFS and DDFS were 91.7% and 93.7%, respectively. Of the 127 pts that received CT, 38 pts (29.9%) achieved pCRB. Among these, 4 relapses (1 metastatic, 1 contralateral recurrence, 1 ILR and 1 in situ recurrence) were observed. Among the 89 pts with no pCRB, 9 relapses (8 metastatic events and 1ILR) were observed. Of the 12 patients who did not receive CT, 6 (50%) pts achieved a pCRB, and no relapse events were observed. Tumor stage was associated with DDFS (p=0.032) but not with DFS. Of the 44, 88 and 7 pts with stage I, II and III tumors; 1, 6, and 2 distant relapses were observed, respectively. pCRB, intrinsic subtype or TILs were not associated with DFS or DDFS.
Conclusions
Despite the small sample size, PAMELA opens the door to study dual HER2 blockade without chemotherapy in selected pts. Achieving pCRB was not associated with survival in this exploratory analysis.
Clinical trial identification
NCT01973660.
Legal entity responsible for the study
SOLTI Cancer Research Group.
Funding
Novartis.
Disclosure
T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly. M. Oliveira: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Seattle Genetics; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Guardant Health; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Genentech; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: GSK; Financial Interests, Institutional, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Institutional, Invited Speaker: Zenith Epigenetics; Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Invited Speaker: SOLTI Breast Cancer Research. J. Cortés: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Cellestia; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Erytech; Financial Interests, Personal, Advisory Board: Athenex; Financial Interests, Personal, Advisory Board: Polyphor; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: LEUKO; Financial Interests, Personal, Advisory Board: Bioasis; Financial Interests, Personal, Advisory Board: Clovis oncology; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Samsung Bioepis; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Ellipses; Financial Interests, Personal, Advisory Board: Hibercell; Financial Interests, Personal, Advisory Board: BioInvent; Financial Interests, Personal, Advisory Board: Gemoab; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Ariad Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires; Financial Interests, Institutional, Research Grant: Bayer healthcare; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Guardanth Health; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma B; Financial Interests, Institutional, Research Grant: Queen Mary University of London; Other, Travel cost and expenses: Roche; Other, Travel cost and expenses: Novartis; Other, Travel cost and expenses: Eisai; Other, Travel cost and expenses: Daiichi Sankyo. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Contracted research: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Amgen; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Amgen; Financial Interests, Personal, Invited Speaker, Lecture fees: BMS; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: BMS; Financial Interests, Personal, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: NanoString; Financial Interests, Institutional, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: Novartis; Financial Interests, Institutional, Other, Contracted research: Roche; Financial Interests, Institutional, Other, Contracted research: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Contracted research; Financial Interests, Personal, Invited Speaker, Lecture fees: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Puma; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Oncolytics; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: MSD; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Guardan Health; Financial Interests, Personal, Expert Testimony, Advisory role/consultancy: Peptomyc; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Lilly; Financial Interests, Institutional, Other, Clinical trials: Lilly; Financial Interests, Institutional, Other, Contracted research: Boehringer; Financial Interests, Institutional, Other, Contracted research: Sysmex Europa GmbH; Financial Interests, Institutional, Other, Contracted research: Medica Scientia inno. Research; Financial Interests, Institutional, Other, Contracted research: Celgene; Financial Interests, Institutional, Other, Contracted research: Astellas; Financial Interests, Institutional, Other, Clinical trials: Roche; Financial Interests, Institutional, Other, Clinical trials: Amgen; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Institutional, Other, Clinical trials: Boehringer; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation. All other authors have declared no conflicts of interest.
205TiP - ATRACTIB: A Phase 2 Trial of First-Line (1L) Atezolizumab (A) in Combination with Paclitaxel (P) and Bevacizumab (B) in Metastatic Triple-Negative Breast Cancer (mTNBC) (ID 213)
- Antonio Llombart Cussac (Valencia, Spain)
- Alfonso Cortes Salgado (Madrid, Spain)
- Jose Manuel Perez Garcia (Barcelona, Spain)
- Silvia Patricia Cortez Castedo (Madrid, Spain)
- Maria Gion Cortes (Madrid, Spain)
- Serafin Morales Murillo (Alpicat, Spain)
- Isabel Blancas López-Barajas (Granada, Spain)
- Salvador Blanch (Valencia, Spain)
- Isabel Calvo Plaza (Madrid, Spain)
- Nieves Diaz Fernandez (Alicante, Spain)
- Frederik Marmé (Mannheim, Germany)
- Alejandro Martinez Bueno (Barcelona, Spain)
- Maria Teresa Taberner Bonastre (Valencia, Spain)
- Michelino De Laurentiis (Napoli, Italy)
- Manuel Ruiz Borrego (Seville, Spain)
- Peter Schmid (London, United Kingdom)
- Valentina Guarneri (Padova, Italy)
- Joseph Gligorov (Paris, France)
- Miguel Sampayo-Cordero (Barcelona, Spain)
- Javier Cortes (Madrid and Barcelona, Spain)
Abstract
Background
The IMpassion130 and KEYNOTE-355 trials have established a substantial benefit from adding an immune checkpoint inhibitor (ICI) to 1L chemotherapy (CT) for mTNBC with programmed death-ligand 1 (PD-L1)–positive tumors. However, many patients (pts) still have a poor outcome with a high unmet medical need. Preclinical and small ongoing clinical studies in TNBC provided encouraging results on the synergism between ICIs, vascular endothelial growth factor (VEGF)-targeted agents, and standard CT without adding significant toxicity. ATRACTIB is evaluating the safety and efficacy of A (anti-PD-L1 antibody) combined with P and B (a VEGF-targeted drug) as 1L regimen for mTNBC pts irrespective of PD-L1 status.
Trial design
ATRACTIB is an international, investigator-initiated, open-label, single-arm, phase 2 trial (NCT04408118). Pts aged ≥18 years, with unresectable locally advanced or mTNBC, Eastern Cooperative Oncology Group performance status of 0–1, who had received no prior systemic therapy or ≥12 months since (neo)adjuvant taxane-based CT are eligible. Pts receive A (840 mg IV, days 1, 15) with P (90 mg/m2 IV, days 1, 8, 15), and B (10 mg/kg IV, days 1, 15) on each 28-day cycle until disease progression, unacceptable toxicity, or patient withdrawal. The primary endpoint is investigator-assessed progression-free survival (PFS) as per RECIST v.1.1. Secondary efficacy endpoints include objective response rate (ORR), clinical benefit rate, time until response, response duration, overall survival, and best percentage change in the sum of the diameters of measurable tumors; safety and tolerability as per NCI-CTCAE v.5.0. Exploratory endpoints are PFS and ORR as per immune-related RECIST, and analysis of predictive biomarkers. The primary analysis consists of median PFS estimation (H0: ≤7 months; H1: ≥9.5 months) based on the exponential maximum likelihood estimation test. A sample size of 100 pts is needed to attain 80% power at a nominal one-sided α level of 5%. An interim analysis is planned for assessing the safety and feasibility in the first 20 pts who have completed a 3-month follow-up or reached the end of study. This trial was opened to accrual in October 2020.
Clinical trial identification
NCT04408118.
Legal entity responsible for the study
MEDSIR S.L.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
A. Cortés Salgado: Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Advisory Role: Clovis, Pfizer, GSK, Roche; Financial Interests, Personal, Speaker’s Bureau: GSK, AstraZeneca, MSD; Financial Interests, Personal, Other, Travel: Daiichi; Financial Interests, Personal, Ownership Interest: Co-Founder: ONCARE. J.M. Perez Garcia: Financial Interests, Personal, Advisory Board: Lilly, Roche, Eisai, Daiichi Sankyo, AstraZeneca, Seattle Genetics; Financial Interests, Personal, Other, Travel: Roche. I. Blancas López-Barajas: Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Novartis, Eisai, Celgene, Pfizer, Lilly, Pierre, Fabre, Bristol Myers Squibb, Kiowa-kirin, Veracyte. P. Schmid: Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Eisai, Celgene; Financial Interests, Institutional, Research Grant: Astellas AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation; Financial Interests, Personal, Other, Employee/ Spouse: Roche. V. Guarneri: Financial Interests, Personal, Advisory Role: Eli Lilly, Novartis, Roche, MSD, Gilead; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, Novartis, GSK; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Roche, Nerviano, Eli Lilly, Merck, Novartis; Financial Interests, Personal, Royalties: Pending (HER2 DX), Reveal Genomics. J. Gligorov: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Daiichi, Eisai, Genomic Health, Immunomedics, Ipsen, Macrogenics, MSD, Novartis, Onxeo, Pfizer, Roche Genentech, Seagen; Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi, Eisai, Genomic Health, Immunomedics, Ipsen, Macrogenics, MSD, Novartis, Onxeo, Pfizer, Roche Genentech, Seagen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Daiichi, Eisai, Genomic Health, Immunomedics, Ipsen, Macrogenics, MSD, Novartis, Onxeo, Pfizer, Roche Genentech, Seagen; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi, Eisai, Genomic Health, MSD, Novartis, Pfizer, Roche Genentech; Financial Interests, Personal, Expert Testimony: AstraZeneca, Daiichi, Eisai, Genomic Health, Immunomedics, Ipsen, Macrogenics, MSD, Novartis, Onxeo, Pfizer, Roche Genentech, Seagen; Financial Interests, Personal, Other, Travel: AstraZeneca, Daiichi, Eisai, Genomic Health, MSD, Novartis, Pfizer, Roche Genentech, Seagen. M. Sampayo-Cordero: Financial Interests, Personal, Other, Honoraria: MEDSIR, Syntax for Science, Optimapharm, Ability Pharma; Financial Interests, Personal, Research Grant: MEDSIR; Financial Interests, Personal, Other, Travel: MEDSIR, Syntax for Science, Optimapharm, and Roche; Financial Interests, Personal, Other, Consultant: MEDSIR, Syntax for Science, and Optimapharm; Financial Interests, Personal, Speaker’s Bureau: MEDSIR; Financial Interests, Personal, Full or part-time Employment: MEDSIR. A. Llombart Cussac: Financial Interests, Personal, Project Lead: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD; Financial Interests, Personal, Stocks/Shares: MedSIR, Initia-Research; Financial Interests, Personal, Advisory Role: Lilly, Roche, Pfizer, Novartis, Pierre Fabre, GenomicHealth, GSK; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, MSD; Financial Interests, Personal, Research Grant: Roche, Foundation Medicine, Pierre Fabre, Agendia; Financial Interests, Personal, Other, Travel: Roche, Lilly, Novartis, Pfizer, AstraZeneca. J. Cortés: Financial Interests, Personal, Advisory Role: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks; Financial Interests, Personal, Other, honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Pharmaceuticals, Leuko (relative); Financial Interests, Personal, Other, travel: Roche, Novartis, Eisai, pfizer, Daiichi Sankyo, AstraZeneca. All other authors have declared no conflicts of interest.