Alfonso Cortes Salgado (Madrid, Spain)
Hospital Universitario Ramón y CajalAuthor Of 2 Presentations
177P - Low HER2 expression does not influence prognosis in metastatic triple-negative breast cancer: results from an international, multicenter analysis coordinated by the Austrian Group Medical Tumor Therapy (AGMT) (ID 185)
- Simon Peter Gampenrieder (Salzburg, Austria)
- Vincent Dezentjé (Amsterdam, Netherlands)
- Matteo Lambertini (Genoa, Italy)
- Alexandre De Nonneville (Marseille, France)
- Maximilian Marhold (Vienna, Austria)
- Fanny Le Du (Rennes, France)
- Cristina Saavedra Serrano (Madrid, Spain)
- Diogo Alpuim Costa (Lisbon, Portugal)
- Eva Blondeaux (Genova, Italy)
- Lucia Del Mastro (Genova, Italy)
- François Bertucci (Marseille, France)
- Anthony Gonçalves (Marseille, France)
- Rupert Bartsch (Vienna, Austria)
- Antoine Deleuze (Rennes, France)
- Alfonso Cortes Salgado (Madrid, Spain)
- Marina Vitorino (Amadora, Portugal)
- Christoph Tinchon (Leoben, Austria)
- Ladislav Pecen (Prague, Czech Republic)
- Gabriel Rinnerthaler (Salzburg, Austria)
- Richard Greil (Salzburg, Austria)
Abstract
Background
Triple-negative breast cancer (TNBC) is associated with poor prognosis. Therefore, new treatment options are urgently needed. About 35% of triple-negative primary tumors show a low expression of HER2 (HER2-low), a potential target for anti-HER2-drugs currently under investigation. In contrast to early breast cancer, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC.
Methods
In this international, multicenter analysis, we retrospectively evaluated TNBC patients from five European countries (Austria, France, Italy, Portugal, and Spain). Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years prior to metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ and lack of HER2 gene amplification measured by in-situ hybridization. HER2-0 was defined as IHC 0+. Univariable survival probabilities were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable hazard ratios were estimated by Cox regression models.
Results
In total, 691 patients, diagnosed between Jan/2006 and Feb/2021, were evaluable. The incidence of HER2-low was 32.0% (95%CI 28.5-35.5%), with similar proportions in samples from metastatic sites (n=265; 29.8%; 95%CI 24.3-35.3%) and primary tumors (n=425; 33.4%; 95%CI 28.9-37.9%; P=0.324). Median OS in HER2-low and HER2-0 TNBC was 18.6 months (95% CI 16.5-20.3) and 16.1 months (95% CI 14.5-18.6), respectively, which was not statistically significantly different (HR 1.00; 95%CI 0.83-1.19; P=0.969). Similarly, in multivariable analysis HER2-low had no significant impact on OS (HR 0.95; 95%CI 0.79-1.13; P=0.545). In addition, we did not identify a difference in prognosis between HER2 IHC 0/1+ and IHC 2+ tumors (median OS 16.8 vs. 18.2 months; HR 0.89; 95%CI 0.69-1.17; P=0.414).
Conclusions
In this dataset of metastatic TNBC, the largest published until now, the frequency of HER2-low was 32.0%, which is similar as reported in early TNBC populations. In contrast to the early stages, HER2-low did not influence OS in metastatic TNBC.
Legal entity responsible for the study
Austrian Study Group of Medical Tumor Therapy (AGMT).
Funding
Austrian Study Group of Medical Tumor Therapy (AGMT), Grant for statistics by Daiichy Sankyo.
Disclosure
S.P. Gampenrieder: Financial Interests, Personal, Invited Speaker: Travel Grant; Financial Interests, Personal, Advisory Board: Novartis, Roche, BMS, AstraZeneca, MSD, Pfizer, Lilly, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Other, Travel Grant: Roche, Amgen, Shire, Novartis, Pfizer, Bayer, Celgene, Daiichi Sankyo. V. Dezentjé: Financial Interests, Personal, Other, Honoraria: Roche, Daiichi Sankyo. M. Lambertini: Financial Interests, Personal, Other, Honoraria: Roche, Sandoz, Takeda, Pfizer, Eli Lilly, and Novartis; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Eli Lilly, and Novartis. A. de Nonneville: Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Lilly; Financial Interests, Institutional, Other, Travel Grant: Amgen, Daiichi Sankyo. M. Marhold: Financial Interests, Personal, Other, Honoraria: Roche, Eli Lilly, Novartis, AstraZeneca, Daiichi Sankyo, Pfizer, MSD, Medmedia; Financial Interests, Personal, Advisory Board: Roche, Lilly, Novartis, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Other, Travel grant: Amgen, Roche, Novartis, Pierre Fabre, Daiichi Sankyo. F. Le Du: Financial Interests, Personal, Other, Honoraria: Novartis, Roche, Daiichi, Pfizer, Lilly, Seagen, Sandoz, AMGEN; Financial Interests, Personal, Advisory Board: Novartis, Roche, Daiichi, Pfizer, Lilly, Seagen, Sandoz; Financial Interests, Personal, Other, Travel Grant: Novartis, Roche, Daiichi, Pfizer, Lilly, Seagen, Pierre Fabre, Amgen. C. Saavedra Serrano: Financial Interests, Personal, Other, Travel Grant: Lilly, Pfizer. D. Alpuim Costa: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Merck KGaA, Novartis, NTT DATA, Pfizer, Uriage; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Novartis, Pfizer; Financial Interests, Personal, Research Grant: Cuf Oncologia, AstraZeneca; Financial Interests, Personal, Other, Travel Grant: Daiichi Sankyo, Merck KGaA, Merck Sharp & Dohme, Novartis, OM Pharma; Financial Interests, Personal, Full or part-time Employment: NTT DATA. L. Del Mastro: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Pfizer, MSD, Genomic Health, Takeda, Ipsen, Eisai, Eli Lilly and Celgene. F. Bertucci: Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Lilly. A. Gonçalves: Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Lilly; Financial Interests, Personal and Institutional, Other, Travel Grant: Novartis. R. Bartsch: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen; Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; Financial Interests, Personal, Research Grant: Daiichi Sankyo, MSD, Novartis, Roche; Financial Interests, Personal, Other, Travel Grant: Roche, Daiichi Sankyo, Lilly, Pfizer. A. Cortés Salgado: Financial Interests, Personal, Other, Honoraria: GSK, AstraZeneca, Roche, MSD, Eisai; Financial Interests, Personal, Advisory Board: Clovis, Lilly, Pfizer, GSK, Ferrer, Roche; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Other, Travel Grant: Roche, Daiichi Sankyo, Pfizer. L. Pecen: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, SOTIO Biotech, Beckman-Coulter. G. Rinnerthaler: Financial Interests, Personal, Other, Honoraria: Roche, Gilead, Pfizer, Eli Lilly, Novartis; Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Pierre Fabre, Eli Lilly, MSD, Novartis, Amgen, Merk. R. Greil: Financial Interests, Personal, Other, Honoraria: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen C., MSD, Merck, Gilead, Daiichi Sankyo, Sanofi, Pfizer; Financial Interests, Personal, Advisory Board: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen C., MSD, Merck, Gilead, Daiichi Sankyo, Sanofi, Pfizer; Financial Interests, Personal, Other, Travel Grant: Roche,Amgen,Janssen,AstraZeneca. 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.