Antonio Llombart Cussac (Valencia, Spain)
Hospital Arnau de VilanovaAuthor Of 4 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.
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.
Presenter Of 1 Presentation
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.