257P - Health-related quality of life (HRQoL) in the ASCENT study of sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC)

Background

SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to SN-38 via a proprietary hydrolyzable linker. In the ASCENT intention-to-treat analysis, SG significantly prolonged progression-free survival (PFS; median 4.8 vs 1.7 mo) and overall survival (OS; median 11.8 vs 6.9 mo) vs single-agent chemotherapy of physician’s choice (TPC) in the second line or greater (2L+) mTNBC setting. Here we assess the impact of SG on HRQoL in the ASCENT study.

Methods

Patients (Pts) with mTNBC who received ≥2 prior systemic therapies (at least 1 for metastatic disease) were randomized to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine). HRQoL was assessed at baseline (BL), before each cycle, and at end of treatment (Tx) using the EORTC QLQ-C30. The HRQoL analysis included all pts with valid HRQoL assessments at BL and at ≥1 post-BL visit. Linear mixed-effect models for repeated measures were calculated using on-Tx data for cycles 2 to 6 (where n was ≥25 in both arms) to estimate differences in overall least-square (LS) mean changes from BL between Tx arms.

Results

The HRQoL analysis included 419 (236 SG; 183 TPC) pts (median age, 54 y; median prior regimens, 4; brain metastases present, 11%). Mean QLQ-C30 subscale scores at BL were similar between Tx arms. SG showed significantly and meaningfully greater improvement than TPC (Table) in global health status (GHS, 0.7 vs -3.4), physical (1.3 vs -4.4) and emotional functioning (3.3 vs. -0.5), and lower symptomatic impact of fatigue (2.0 vs 7.1), pain (-8.9 vs -1.9), dyspnea (-3.8 vs 4.0), and insomnia (-4.7 vs 0.3). Of all symptoms, only diarrhea was significantly and meaningfully worse with SG (14.1 vs. -1.3).

Conclusions

In pts with 2L+ mTNBC, SG not only prolonged PFS and OS but also improved HRQoL vs TPC. Although symptoms of diarrhea were worse with SG, this did not seem to translate to an adverse impact on pts’ global health score or functioning. Table: 257P

Differences in overall LS mean changes from baseline (95% CI)

* p<0.05, ** p<0.01^aMID=minimum important difference for improvement (Cocks et al., 2011)

Clinical trial identification

NCT02574455.

Editorial acknowledgement

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

S. Loibl: Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: AbbVie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Novartis, Pfizer, Roche, Teva, Vifor; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Other: AbbVie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Novartis, Pfizer, Roche, BMS, Eirgenix, Lilly, Merck, MSD, Seagen, Prime/Medscape, Puma, Samsung, Pierre Fabre; Financial Interests, Personal, Other, lecture: Chugai. D. Loirat: Financial Interests, Personal, Other, Consulting fees: MSD, Novartis, AstraZeneca, Roche, Immunomedics, Pfizer; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, MSD, Lilly, Novartis, BMS, Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche, MSD, AstraZeneca, Novartis; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: MSD. S.M. Tolaney: Financial Interests, Personal and Institutional, Other, PI of studies(all funding to institute); Honorarium for consultant/advisory board: Immunomedics/Gilead; Financial Interests, Personal and Institutional, Other, PI of studies(all funding to institute); Honorarium for consultant/advisory board: AstraZeneca, Eli Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Bristol Myers Squibb, Eisai, Nanostring, Sanofi, Odonate, Immunomedics/Gilead; Financial Interests, Institutional, Other, PI of study (all funding to institute): Exelixis, Cyclacel; Financial Interests, Personal, Other, Honorarium for consulting: Seattle Genetics, AbbVie, Athenex, CytomX; Financial Interests, Personal, Advisory Board, Honorarium for Advisory Board: Puma, Celldex, Silverback Therapeutics, G1 Therapeutics, OncoPep, Kyowa Kirin Pharmaceuticals, Daiichi Sankyo, Samsung Bioepsis Inc., Certara, Mersana Therapeutics. K. Punie: Financial Interests, Institutional, Other, Consulting fees- Payments made to institution: Roularta, Novartis, Roche, Medscape, Vifor Pharma, Pfizer, Pierre Fabre; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events- Payment made to institution: Lilly, McCann Health, Mundi Pharma, MSD, Novartis, Pfizer, Roche; Financial Interests, Institutional, Other, Support for attending meetings and/or travel- Payment made to institution: Astrazeneca, Novartis, PharmaMar, Roche, Pfizer; Financial Interests, Institutional, Other, Participation on a Data Safety Monitoring Board or Advisory Board- Payment made to institution: Astrazeneca, Novartis, Lilly, Roche, Pierre Fabre, Vifor Pharma; Financial Interests, Personal, Advisory Board, BSMO Board member of Belgian Society of Medical Oncology: BSMO; Financial Interests, Personal, Other, Committee member of ESMO Young Oncologists Committee: ESMO; Financial Interests, Institutional, Funding, Research funding to institution: Sanofi. M. Oliveira: Financial Interests, Institutional, Invited Speaker: Roche, Genentech, PUMA Biotechnology, AstraZeneca, Seattle Genetics, Boehringer Ingelheim, Novartis; Financial Interests, Personal, Invited Speaker, Personal Fees: Roche, Genentech, PUMA Biotechnology, AstraZeneca, Seattle Genetics, Novartis; Non-Financial Interests, Personal, Invited Speaker: Roche, Pierre-Fabre, Eisai, GP Pharma, Grunenthal, Novartis; Financial Interests, Personal, Invited Speaker, Grant to conduct clinical trial: Immunomedics. H.S. Rugo: Financial Interests, Institutional, Funding, Funding for Sponsored studies to UCSF: Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi, Seattle Genetics, Eisai, Macrogenics, Sermonix, Immunomedics, AstraZeneca; Non-Financial Interests, Personal, Other, Travel Support for Educational Meeting: Daiichi, Mylan, Pfizer, Merck, Novartis, AstraZeneca, Macrogenics; Financial Interests, Personal, Other, Honoraria: Mylan, Puma, Samsung. A. Bardia: Financial Interests, Institutional, Research Grant, Research Grant to Institution: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics; Financial Interests, Personal, Other, Advisory Board/Consulting: Biothernostics Inc., Diiachi Pharma/AstraZeneca, Puma, Eli Lilly, Foundation Medicine; Financial Interests, Personal, Other, Advisory Board/Consulting; Steering Committee. Travel support: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics; Financial Interests, Personal, Other, Advisory Board/Consulting. Travel support: Taiho, Sanofi, Phillips. S.A. Hurvitz: Financial Interests, Institutional, Other, Contracted Research: Ambrx, Amgen, AstraZeneca, Arvinas, Bayer, Daiichi Sankyo, Genentech/Roche, Gilead, GSK, Immunomedics, Lilly, Macrogenics, NovarUs, Pfizer, OBI Pharma, Pieris, PUMA, Radius, Sanofi, SeaFle GeneUcs, Dignitana, Zymeworks, Phoenix Molecular Designs, Ltd.; Financial Interests, Personal, Stocks/Shares, Stock Options: NK Max. A. Brufsky: Financial Interests, Personal, Other, support for the present manuscript: Immunomedics (Gilead); Financial Interests, Personal, Other, Consulting fees: Immunomedics (Gilead), Novartis, Genentech, Roche, Eisai, Merck, Athenex. K. Kalinsky: Financial Interests, Personal, Research Grant: Inctye, Novasrtis, Genentech, Lilly, Pfizer, Calithera, immunomedics, Acetylon, Seattle Genetics, Amgen, Zeno, Cytomx; Financial Interests, Personal, Other, Consulting fees: Lilly, Pfizer, Novartis, Eisai, AstraZeneca, Genentech, immumomedics, merck, seattle genetics, cyclacel, oncosec; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Lilly; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Lilly, AstraZeneca, Pfizer; Non-Financial Interests, Personal, Other, Steering Committee: Immunomedics, AstraZeneca, Genentech; Financial Interests, Personal, Other, Spouse (employee): Grail, Array, Pfizer. J. Cortés: Financial Interests, Personal, Other, Consulting/Advisor: Roche+, Celgene -, Celestial, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme +, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Kyowa Kirin; Financial Interests, Personal, Other, Honoraria: Roche +, Novartis +, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo; Financial Interests, Institutional, Funding, Research funding to the Institution: 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, Stock, patents and intellectual property: MedSIR; Financial Interests, Personal, Other, Travel, accommodation, expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo. J. O'Shaughnessy: Financial Interests, Personal, Other, Consulting fees: AbbVie Inc.; Agendia; Amgen Biotechnology; Aptitude Health; AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Eisai; G1 Therapeutics; Genentech; Immunomedics; Ipsen Biopharmaceuticals; Lilly; Merck; Myriad; Novartis; Ondonate Therapeutics; Pfizer; . V.C. Dieras: Financial Interests, Personal, Other, Honoraria: Roche/Genentech, Novartis, Lilly, Pfizer, AstraZeneca, Eisai, AbbVie, MSD, Daiichi Sankyo, Seattle Genetics; Financial Interests, Personal, Other, Consulting or Advisory Role: Roche/Genentech, Novartis, Lilly, Pfizer, AstraZeneca, Eisai, AbbVie, MSD, Daiichi Sankyo, Seattle Genetics; Financial Interests, Personal, Speaker’s Bureau: Symposium/Roche, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Roche, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo. L.A. Carey: Financial Interests, Institutional, Other, Participation on a Data Safety Monitoring Board or Advisory Board- Dr. Carey has not been compensated for any of these relationships. Compensation has been to UNC-CH and Dr. Carey has no signatory authority over any UNC account: Sanofi Aventis, Novartis, Genentech/Roche GSK, AstraZeneca/Daiichi Sankyo Aptitude Health; Financial Interests, Personal, Advisory Board, Spouse serves on board: uncompensated- Spouse on board – not Dr. Lisa Carey: Falcon Therapeutics, neural stem cell therapy patent. L. Gianni: Financial Interests, Institutional, Research Grant, support for research projects to Institution: Zymeworks, Revolution Medicines; Financial Interests, Personal, Other, Consulting fees: Forty Seven (CD47), Genenta, METIS Precision Medicine, Novartis, Odonate Therapeutics, Revolution Medicines, Synaffix, Zymeworks, Menarini Ricerche, Amgen, Biomedical Insights Inc.; Financial Interests, Personal, Other, Speaker at Roche Products Taiwan meeting: Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Pfizer; Financial Interests, Personal, Other, Co-inventor of “European patent Application N. 12195182.6 and 12196177.5” titled PDL-1 expression in anti-HER2 therapy-Roche – Issued: N/A; Financial Interests, Personal, Advisory Board: ADC Therapeutics, Astrazeneca, Celgene, Eli Lilly, G1 Therapeutics, Genentech, Genomic Health, Merck Sharp & Dohme, Oncolytics Biotech, Odonate Therapeutics, Onkaido Therapeutics, Roche, Pfizer, Taiho Pharmaceutical, Hexal Sandoz, Seattle Genetics, Syntho. M. Gharaibeh: Financial Interests, Personal, Other, Personal Fees: Gilead Sciences. L. Moore: Financial Interests, Personal, Invited Speaker: Gilead Sciences. L. Shi: Financial Interests, Institutional, Invited Speaker, Evidera received payment for statistical analysis for this project: Gilead Sciences. M. Piccart: Financial Interests, Institutional, Research Grant, To my institute: AstraZeneca, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon; Financial Interests, Personal, Other, Scientific Board: Oncolytics; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Camel-IDS, Debiopharm, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Pfizer, Roche-Genentech, Seattle Genetics, Immutep.