Jose Manuel Perez Garcia (Barcelona, Spain)
Quiron GroupAuthor Of 5 Presentations
14P - Gut and oral microbiota profiling in patients (pts) with hormone receptor-positive (HR+) metastatic breast cancer (MBC) receiving pembrolizumab (P) plus eribulin (E): CALADRIO (ID 32)
- Nancy Teng (Norwich, United Kingdom)
- Matthew J. Dalby (Norwich, United Kingdom)
- Raymond Kiu (Norwich, United Kingdom)
- Tim Robinson (Bristol, United Kingdom)
- Maria Gion Cortes (Madrid, Spain)
- Begona Bermejo De Las Heras (Valencia, Spain)
- Jose Manuel Perez Garcia (Barcelona, Spain)
- Lourdes Calvo-Martinez (A Coruña, Spain)
- Aleix Prat (Barcelona, Spain)
- Raul Marquez Vazquez (Madrid, Spain)
- Manuel Ruiz Borrego (Seville, Spain)
- Susana De la Cruz (Pamplona, Spain)
- Antonio Llombart Cussac (Valencia, Spain)
- Giuseppe Curigliano (Milan, Italy)
- Peter Schmid (London, United Kingdom)
- Mario Mancino (Valencia, Spain)
- Lindsay Hall (Norwich, United Kingdom)
- Stephen Robinson (Norwich, United Kingdom)
- Javier Cortes (Madrid and Barcelona, Spain)
- Andrea Malfettone (Barcelona, Spain)
Abstract
Background
Changes occurring in host-associated microbial communities (i.e. microbiota) may modulate responses to checkpoint blockade immunotherapy. We previously showed that anti-programmed cell death 1 protein P added to microtubule-targeting chemotherapy E has an encouraging antitumor activity in HR+ MBC pts regardless of programmed death-ligand 1 status. The CALADRIO study assessed the impact of gut and oral microbiota on clinical outcome of pts from the KELLY trial.
Methods
The phase 2 KELLY trial investigated the efficacy and safety of P plus E in 44 pts with pre-treated, HR+, HER2-negative, locally recurrent inoperable or MBC (NCT03222856). Fecal and saliva samples were prospectively collected at baseline (BL), after 3 cycles, and end of treatment from a subset of pts. Tumor response was grouped into clinical benefit (CB; complete or partial responses, or stable disease [SD] ≥24 weeks) and no CB (SD <24 weeks or progressive disease) as per RECIST 1.1. Shotgun metagenomic and 16S rRNA gene sequencing were used to characterize fecal and saliva microbiota profiles, respectively. Microbiota data were analyzed using MEGAHIT, LEfSe, Wilcoxon ranked sum, and PERMANOVA methods.
Results
A total of 58 fecal and 68 saliva samples were collected. Overall P+E did not cause significant gut or oral microbiota perturbations, indicating any drug-related microbial toxicity. Across all pts, dominant gut microbiota genera included Bacteroides and Faecalibacterium, with a common oral microbe, Prevotella, also present. LeFSe analysis suggested CB was driven in part by gut-associated Bacteroides fragilis and oral-associated Streptococcus with an abundance ≥50%. Pts experiencing CB had gut and oral microbiota richness at BL and a decrease over treatment potentially related to the antibiotic usage. Several typical oral microbes in both saliva and fecal samples were also observed, suggesting a potential translocation along the oral-gut axis.
Conclusions
These preliminary findings suggest potential avenues for downstream microbiota pts stratification before commencement of treatment. Further investigation is required in larger cohorts.
Clinical trial identification
NCT03222856.
Legal entity responsible for the study
MEDSIR.
Funding
MEDSIR.
Disclosure
M. Gion Cortes: Financial Interests, Personal, Sponsor/Funding: Roche; Financial Interests, Personal, Sponsor/Funding: Pfizer. J.M. Perez Garcia: Non-Financial Interests, Personal, Advisory Role: Roche; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Sponsor/Funding: Roche. A. Prat: Non-Financial Interests, Personal, Full or part-time Employment: Novoartis; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Sponsor/Funding: Pfizer, Novartis, Roche, MSD Oncology, Lilly, Daiichi Sankyo, Amgen, Guardant Health; Non-Financial Interests, Personal, Advisory Role: Amgen, Roche, Novartis, Pfizer, Bristol Myers Squibb, Boehringer, Puma, Oncolytics Biotech, Daiichi Sankyo, AbbVie, AstraZeneca, NanoString Technologies (to the Institution); Financial Interests, Institutional, Funding: Roche, Novartis, Incyte, Puma Biotechnology; Financial Interests, Personal, Ownership Interest: Patents:- PCT/EP2016/080056, - WO/2018/096191, US 63/023785, HER2DX (filing); Financial Interests, Personal, Sponsor/Funding: Daiichi Sankyo; Other, Personal, Other: Oncolytics, Peptomyc S.L. A. Llombart Cussac: Non-Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD;; Financial Interests, Personal, Stocks/Shares: MEDSIR, Initia-Research; Non-Financial Interests, Institutional, Advisory Role: Lilly, Roche, Pfizer, Novartis, Pierre Fabre, GenomicHealth, GSK; Non-Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, MSD; Financial Interests, Personal, Funding: Roche, Foundation Medicine, Pierre Fabre, Agendia; Financial Interests, Personal, Sponsor/Funding: Roche, Lilly, Novartis, Pfizer, AstraZeneca. M. Mancino: Financial Interests, Personal and Institutional, Full or part-time Employment: MEDSIR. J. Cortés: Non-Financial Interests, Personal, Advisory Role: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology.; Financial Interests, Personal, Sponsor/Funding: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo.; Financial Interests, Personal and Institutional, Funding: 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. A. Malfettone: Financial Interests, Personal and Institutional, Full or part-time Employment: MEDSIR. All other authors have declared no conflicts of interest.
93MO - Optimal 18F-FDG PET/CT (FDG-PET) cut-off for pathological complete response (pCR) prediction in HER2-positive [HER2+] early breast cancer (EBC) patients (pts) treated with neoadjuvant trastuzumab (T) and pertuzumab (P) in PHERGain trial (ID 8)
- Géraldine Gebhart (Brussels, Belgium)
- Marleen Keyaerts (Jette, Belgium)
- Thomas Guiot (Brussels, Belgium)
- Patrick Flamen (Brussels, Belgium)
- Manuel Ruiz Borrego (Seville, Spain)
- Agostina Stradella (L'Hospitalet de Llobregat, Spain)
- Begona Bermejo De Las Heras (Valencia, Spain)
- Santiago Escriva de Romani (Barcelona, Spain)
- Lourdes Calvo-Martinez (A Coruña, Spain)
- Nuria Ribelles Entrena (Malaga, Spain)
- Noelia Martinez (Madrid, Spain)
- Cinta Rosa Albacar Miro (Reus, Spain)
- Marco A. Colleoni (Milan, Italy)
- Manuel Atienza de Frutos (Villaviciosa de Odón, Spain)
- Miguel Sampayo-Cordero (Barcelona, Spain)
- Javier Cortes (Madrid and Barcelona, Spain)
- Jose Manuel Perez Garcia (Barcelona, Spain)
- Antonio Llombart Cussac (Valencia, Spain)
Abstract
Background
PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy (CT) de-escalation in HER2-positive, stage I-IIIA, invasive, operable breast cancer with at least one breast lesion evaluable by FDG-PET. Based on data from NeoALTTO study, FDG-PET “responders” were defined as those pts with maximum standardized uptake value (SUVmax) reduction of at least 40% in all their target lesions after two cycles of T and P. Of the 285 patients included in T+P arm, 227 pts were FDG-PET responders and received a total of 8 cycles of T+P. pCR, defined as pT0/isN0, reached 37.9% (86/227 pts). Here we describe secondary preplanned analysis of the best cut-off of SUVmax reduction for pCR prediction.
Methods
ROC analysis was applied to research the most appropriate deltaSUVmax cut-off in HER2+ EBC pts treated exclusively with neoadjuvant T and P (± endocrine therapy).
Results
The delta SUVmax capability of predicting pCR in terms of AUC was 72.1% (95%CI, 65.1-79.2). The optimal SUVmax reduction cut-off was found to be 77.0%, with a 51.2% sensitivity and a 78.7% specificity for prediction of pCR. Yet, using this cut-off, 32.6% (74/227 pts) would be classified as FDG-PET responders increasing the pCR rate from 37.9% (cut-off ≥40%) to 59.5% (44/74 pts) (p<0.01). With this optimized cut-off 19.4% (44/227 pts) would avoid chemotherapy to achieve a pCR. Subgroup analysis in pts with HER2 immunohistochemistry score 3+ will be reported.
Conclusions
Increased deltaSUVmax cut-off (≥77%) after two cycles of exclusive T+P achieves a pCR rate in the range of control arm with CT+TP in PHERGain (59,5% vs. 57,7%, respectively) selecting a subgroup of pts with HER2 addicted tumors. However, the original cut-off (≥40%) maximizes the number of pts who could avoid CT. The definitive value of pCR in the absence of CT should be confirmed by final DDFS results from PHERGain trial.
Legal entity responsible for the study
Medica Scientia Innovation Research (MEDSIR) Barcelona, Spain and Ridgewood, New Jersey.
Funding
Has not received any funding.
Disclosure
G. Gebhart: Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Funding: Roche. M. Keyaerts: Financial Interests, Institutional, Funding, Precirix; Financial Interests, Personal, Stocks/Shares, Abscint. S. Escriva de Romani: Financial interests, Personal, Invited Speaker: Daiichi Sankyo/AstraZeneca, Pfizer, Roche. Financial interests, Personal, Advisory Board: Daiichi Sankyo/AstraZeneca, Roche, Seagen. Financial interests, Insitutional, Other, Local PI: Byondis, Lilly, MedSIR, Roche, Synthon. M.A. Colleoni: Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Role: Pfizer, OBI Pharma, Celldex; AstraZeneca; Financial Interest, Personal, Research Grant: Roche. M. Atienza de Frutos: Financial Interests, Personal, Full or part-time Employment: Lilly; Financial Interests, Personal, Stocks/Shares: Lilly. M. Sampayo-Cordero: Financial Interests, Personal, Other: MEDSIR, Syntax for Science, Nestle; Financial Interests, Personal, Advisory Board: MEDSIR, Syntax for Science, Nestle; Financial Interests, Personal, Speaker’s Bureau: MEDSIR, Syntax for Science, Nestle, Roche; Financial Interests, Personal, Funding: MEDSIR, Syntax for Science, Nestle, Roche. J. Cortés: Financial Interests, Personal, Advisory Board: 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, Zymeworks, Gemoab, Gilead, Menarini, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires, Roche, Ariad Pharmaceuticals, AstraZeneca, Bayer Healthcare, Eisai, Guardanth Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo. J.M. Perez Garcia: Financial Interests, Personal, Advisory Board: Roche, Eli Lilly; Financial Interests, Personal, Expert Testimony: Eisai. A. Llombart Cussac: Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD; Financial Interests, Personal, Stocks/Shares: MEDSIR, Initia-Research; Financial Interests, Personal, Advisory Board: Lilly, Roche, Pfizer, Novartis, Pierre Fabre, Genomic Health, GSK; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, MSD; Financial Interests, Institutional, Funding: Roche, Foundation Medicine, Pierre Fabre, Agendia; Financial Interests, Personal, Other: Roche, Lilly, Novartis, Pfizer, AstraZeneca. All other authors have declared no conflicts of interest.
102P - Long-term prediction of clinical outcomes by the 21-gene test in HR+ HER2- breast cancer patients with residual disease after neoadjuvant chemotherapy. (ID 114)
- Vicente Peg (Barcelona, Spain)
- Nikaoly De los Ángeles (Barcelona, Spain)
- Begoña Vieites (Seville, Spain)
- Meritxell Bellet (Barcelona, Spain)
- Carolina Castilla (Seville, Spain)
- Patricia Gomez Pardo (Barcelona, Spain)
- Ana Pérez - Luque (Seville, Spain)
- Maria Angeles Lopez (seville, Spain)
- Francisco Javier Salvador Bofill (Seville, Spain)
- Lina Alfaro (Seville, Spain)
- Jose Manuel Perez Garcia (Barcelona, Spain)
- Martin Espinosa-Bravo (Barcelona, Spain)
Abstract
Background
Neoadjuvant chemotherapy (NAC) is increasingly used for treatment of early-stage breast cancer patients, with HR+, HER2- tumors showing the lowest rate of pathological complete response (pCR). Therefore, standardized tools result essential to identify those HR+, HER2- breast cancer patients with residual disease in the breast and/or axillary nodes who are at increased risk of distant recurrence after treatment with NAC.
Methods
A total of 224 patients were retrospectively analyzed using the 21-gene assay (Oncotype DX Breast Recurrence Score ® test). Patients were classified according to test results after NAC (RS>25 or RS≤25) and long-term outcomes determined for each subclass. In addition, results of the 21-gene assay from post-NAC samples and biopsy cores (pre-NAC) were compared to identify changes that occurred after treatment.
Results
- Post-NAC 21-gene test results were strongly associated in the multivariable analysis (controlling for age, tumor size, and nodal status) with distant recurrence risk [HR=2.41 (1.18, 4.76), p=0.0162] and overall survival during the first 5 years [HR=4.96 (1.98, 12.95), p=0.0007]. - Post-NAC 21-gene test results stratified patients into two groups (RS ≤25 and RS >25) showing significant differences in terms of distant recurrence-free survival (long rank p=0.0029) and overall survival (long rank p=0.0007). Patients with RS ≤25 showed an absolute reduction of 19.4% and 16.6% in their risk of distant recurrence at 5 years and 10 years, respectively. In terms of overall survival, the difference between groups was 19.8% and 16.8% at the same time points. - Comparison of 21-gene test results in pre-NAC and post-NAC samples revealed an overall reduction in the biological risk of patients after neoadjuvant treatment (p<.0001).
Conclusions
This is the first study exploring the potential use of the 21-gene assay as a standardized tool for the identification of high vs low biological risk patients which may benefit from additional treatment after NAC. The 21-gene assay could support the personalization of treatment in this group of patients and inform future trial designs.
Legal entity responsible for the study
Dr. Vicente Peg Cámara (Hospital Vall d´Hebrón).
Funding
Genomic Health Inc * a wholly owned subsidiary of Exact Sciences Corporation.
Disclosure
All authors have declared no conflicts of interest.
164O - Health-Related Quality of Life (HRQoL) With Pembrolizumab (pembro) + Chemotherapy (chemo) vs Placebo (pbo) + Chemo as 1L Treatment for Advanced Triple-Negative Breast Cancer (TNBC): Results From KEYNOTE-355 (ID 307)
- David W. Cescon (Toronto, Canada)
- Peter Schmid (London, United Kingdom)
- Hope S. Rugo (San Francisco, United States of America)
- Seock-Ah Im (Seoul, Korea, Republic of)
- Mastura Md Yusof (Kuala Lumpur, Malaysia)
- Carlos E. Gallardo (Providencia, Chile)
- Oleg Lipatov (Republic of Bashkortostan, Russian Federation)
- Carlos H. Barrios (Porto Alegre, Brazil)
- Jose Manuel Perez Garcia (Barcelona, Spain)
- Hiroji Iwata (Nagoya, Japan)
- Norikazu Masuda (Nagoya, Japan)
- Marco Antonio Torregroza Otero (Monteria, Colombia)
- Erhan Gokmen (Izmir, Turkey)
- Sherene Loi (Melbourne, Australia)
- Amin Haiderali (Kenilworth, United States of America)
- Xuan Zhou (North Wales, United States of America)
- Zifang Guo (Kenilworth, United States of America)
- Allison Martin Nguyen (Kenilworth, United States of America)
- Javier Cortes (Madrid and Barcelona, Spain)
Abstract
Background
KEYNOTE-355 (NCT02819518) evaluated pembro + chemo vs pbo + chemo in previously untreated patients (pts) with locally recurrent inoperable or metastatic TNBC. Pembro + chemo improved the PFS and OS in pts with PD-L1 combined positive score (CPS) ≥10 disease. We present results for patient-reported outcome (PRO) measures among pts with PD-L1 CPS ≥10.
Methods
Pts were randomized 2:1 to pembro 200 mg or pbo Q3W for up to 35 cycles + chemo (investigator’s choice of nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin). QLQ-C30 (including global health status/quality of life [GHS/QoL]) and physical and emotional functioning scales), QLQ-BR23, and EQ-5D visual analogue scale (VAS) were prespecified. PROs were assessed at baseline, during treatment, and the 30-day safety follow-up visit and analyzed for pts who received ≥1 dose of study treatment and completed ≥1 PRO assessment. Change in PRO scores from baseline were assessed at wk 15 (latest timepoint at which completion/compliance rates were ≥60%/≥80%; negative values favor the pembrolizumab group). Time to deterioration (TTD) in PROs was defined as time to first onset of ≥10-point worsening in score from baseline.
Results
These PRO analyses included 317 pts with PD-L1 CPS ≥10 (pembro + chemo; n = 217; pbo + chemo, n = 100). Completion/compliance at wk 15 was 77.0%/87.0% with pembro + chemo and 70.0%/81.4% with pbo + chemo. There were no between-group differences in change from baseline to wk 15 in the QLQ-C30 GHS/QoL, emotional functioning, physical functioning, or the EQ-5D VAS scale scores, and no between-group difference in TTD in QLQ-C30 GHS/QoL, emotional functioning, or physical functioning (Table). Analyses by QLQ-BR23 showed no decrease in HRQoL with pembro + chemo vs pbo + chemo. aBased on constrained longitudinal data analysis model (two-sided P value). bBased on stratified Cox regression model; P value based on stratified log-rank test (one-sided).
Change from baseline to wk 15a Between-group difference (pembro vs pbo) QLQ-C30 GHS/QoL −1.81 (−6.92 to 3.30); P = 0.4865 QLQ-C30 emotional functioning −1.43 (−7.03 to 4.16); P = 0.6149 QLQ-C30 physical functioning −1.05 (−6.59 to 4.50); P = 0.7102 EQ-5D VAS 0.18 (−5.04 to 5.39); P = 0.9468 TTDb HR (Pembro vs Pbo) (95% CI); P Value QLQ-C30 GHS/QoL 1.00 (0.72 to 1.40); P = 0.5137 QLQ-C30 emotional functioning 1.28 (0.88 to 1.85); P = 0.9039 QLQ-C30 physical functioning 1.26 (0.90 to 1.77); P = 0.9194
Conclusions
Addition of pembro to chemo did not result in a decrease in HRQoL in pts with previously untreated, PD-L1–positive (CPS ≥10) advanced, TNBC.
Clinical trial identification
NCT02819518, EudraCT 2016-001432-35.
Editorial acknowledgement
Additional support was provided by Wilbur Panof Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Medical writing assistance was provided by Kara Nyberg, PhD, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp.
Funding
Merck Sharp & Dohme Corp.
Disclosure
D.W. Cescon: Financial Interests, Personal, Consultancy/Advisory role: AstraZeneca, Exact Sciences, Eisai, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer Roche; Financial Interests, Institutional, Research Funding: GlaxoSmithKline, Inivata, Merck, Pfizer, Roche; Other: is a member of a trial steering committee for AstraZeneca, Merck and GlaxoSmithKline; Other: holds a holds a patent (US62/675,228) for methods of treating cancers characterized by a high expression level of spindle and kinetochore associated complex subunit 3 (ska3) gene. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche; Other, Spouse - Employee: Roche. H.S. Rugo: Financial Interests, Personal, Invited Speaker: Puma; Financial Interests, Personal, Advisory Board: Samsung; Financial Interests, Personal, Invited Speaker: Mylan; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Odonate; Financial Interests, Institutional, Invited Speaker: Sermonix; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Polyphor; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. S-A. Im: Financial Interests, Personal, Consulting/Advisory role: Amgen, AstraZeneca, Eisai, Hanmi, Lilly, Medpacto, Inc., Novartis, Pfizer, Roche/Genentech; Financial Interests, Personal, Research Funding: AstraZeneca, Pfizer, Roche/Genentech; Financial Interests, Personal, Other, Travel, accommodations, expenses: Novartis; Roche/Genentech; Financial Interests, Personal, Other: Roche. M. Md Yusof: Financial Interests, Personal, Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, MSD, Specialised Therapeutics, Zuellig Pharma, Novartis, Pfizer, Roche, Eisai, Celgene; Financial Interests, Institutional, Research grant: Astellas, AstraZeneca, Arcus, Genentech, Mundi Pharma, Novartis, Pfizer, Roche. C.E. Gallardo: Financial Interests, Personal, Consulting/Advisory role: Lilly, MSD, Roche; Financial Interests, Personal, Speakers Bureau: Bristol Myers Squibb; Financial Interests, Personal, Research Funding: Novartis Pharma SAS, Roche; Financial Interests, Personal, Other, Travel, accommodations, expenses: MSD, Roche. C.H. Barrios: Financial Interests, Personal, Consulting/Advisory role: Boehringer Ingelheim, Eisai Europe Ltd., GlaxoSmithKline, Novartis Pharma SAS, Pfizer Pharmaceuticals Israel, Roche/Genentech; Financial Interests, Personal, Research Funding: AB Science, Abraxis BioScience, Amgen, Asana Biosciences, Astellas Pharma, AstraZeneca, Biomarin, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Exelixis, GlaxoSmithKline, ImClone Systems, Investigator in AbbVie-sponsored cl. Trials, LEO Pharma, Lilly, Medivation, Merck, Merrimack, Millennium, Mylan, Novartis Pharma SAS, Pfizer Pharmaceuticals Israel, Roche/Genentech, Sanofi, Taiho Pharmaceutical. J.M. Perez Garcia: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Expert Testimony: Eisai. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal and Institutional, Invited Speaker: Chugai; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Invited Speaker: Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Sanofi; Financial Interests, Personal and Institutional, Invited Speaker: Lilly; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Bayer; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer; Financial Interests, Personal and Institutional, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Personal and Institutional, Invited Speaker: Behringer; Financial Interests, Personal and Institutional, Invited Speaker: Nihon Kayaku. N. Masuda: Financial Interests, Other, Leadership: Japan Breast Cancer Research Group Association (JBCRG); Financial Interests, Personal, Honoraria: AstraZeneca, Chugai Pharma, Eisai, Lilly Japan, Pfizer; Financial Interests, Institutional, Research Funding: AstraZeneca, Chugai Pharma, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa-Kirin, MSD, Novartis, Pfizer, Sanofi. E. Gokmen: Financial Interests, Other: Eli Lilly, Janssen Oncology, Novartis, Pfizer, Roche; Financial Interests, Personal, Consulting/Advisory Role: Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Speaker Bureau: Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: BMS, MSD Oncology, Novartis, Pfizer, Roche. S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech; Financial Interests, Institutional, Advisory Board, Consultant: Novartis; Financial Interests, Institutional, Advisory Board, Consultant: GlaxoSmithKline; Financial Interests, Institutional, Advisory Board, Consultant: Roche Genentech; Financial Interests, Institutional, Advisory Board, Consultant: AstraZeneca; Financial Interests, Institutional, Advisory Board, Consultant: Silverback Therapeutics; Financial Interests, Institutional, Advisory Board, Consultant: G1 Therapeutics; Financial Interests, Institutional, Expert Testimony, Consultant: Puma Biotechnologies; Financial Interests, Institutional, Expert Testimony, Consultant: Pfizer; Financial Interests, Institutional, Expert Testimony, Consultant: Seattle Genetics; Financial Interests, Institutional, Expert Testimony, Consultant: BMS; Financial Interests, Institutional, Funding, Research: Novartis; Financial Interests, Institutional, Funding, Research: BMS; Financial Interests, Institutional, Funding, Research: Merck; Financial Interests, Institutional, Funding, Research: Puma Biotechnology; Financial Interests, Institutional, Funding, Research: Eli Lilly; Financial Interests, Institutional, Funding, Research: Nektar Therapeutics; Financial Interests, Institutional, Funding, Research: AstraZeneca; Financial Interests, Institutional, Funding, Research: Seattle Genetics; Financial Interests, Institutional, Funding, Research: Roche - Genentech; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Novartis; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Bristol Myers Squibb; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Merck; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): AstraZeneca; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Roche Genentech. A. Haiderali, Z. Guo, A. Martin Nguyen: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Financial Interests, Personal, Ownership Interest, Stock and Other Ownership Interests: Merck & Co., Inc. X. Zhou: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 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: Zymeworks; Financial Interests, Personal, Advisory Board: Gemoab; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Advisory Board: Reveal Genomics; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Ariad Pharmaceuticals; 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, 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. 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.