Abstract 198P
Background
The phase II KEYLYNK-009 (NCT04191135) study evaluated maintenance pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy (chemo) in patients (pts) with metastatic TNBC who had clinical benefit from induction with first-line pembro + chemo. We present patient-reported outcomes (PROs) from this study to provide important evidence on the benefit/risk profile of these treatments.
Methods
Eligible pts received induction therapy with pembro 200 mg Q3W + chemo (carboplatin AUC 2 + gemcitabine 1000 mg/m2 on days 1 and 8 per 21-day cycle) for 4–6 cycles. Pts with CR, PR, or SD were randomized 1:1 to pembro 200 mg Q3W + ola 300 mg BID or pembro + chemo (induction regimen) for up to 35 cycles (including induction). PROs were secondary endpoints and included changes from randomization (baseline) to week 18 (last time with completion/compliance ∼≥60%/80% in QLQ-C30) for EORTC QLQ-C30 GHS/QoL, QLQ-C30 physical and emotional functioning, QLQ-BR23 systemic therapy side effects, and EQ-5D-5L visual analogue scale (VAS). TTD (time from baseline to first onset of a confirmed ≥10-point deterioration) was also assessed. PROs were analyzed in randomized and treated pts who completed ≥1 PRO assessment. No alpha was assigned to PRO analyses.
Results
PRO analyses included 267 pts (pembro + ola, n = 135; pembro + chemo, n = 132). Completion/compliance in QLQ-C30 at week 18 was 59.3%/88.9% with pembro + ola and 62.1%/85.4% with pembro + chemo. No between-group differences were observed, except that TTD for QLQ-C30 GHS/QoL favored pembro + chemo (Table). Table: 198P
| Between-group difference in change from baseline to wk 18 least-squares mean (95% CI)a (Pembro + Ola vs Pembro + Chemo) | |
| QLQ-C30 GHS/QoL | −3.28 (−7.69 to 1.12) |
| QLQ-C30 physical functioning | −0.16 (−4.89 to 4.56) |
| QLQ-C30 emotional functioning | 2.08 (−3.16 to 7.31) |
| QLQ-BR23 systemic therapy side effects | 0.93 (−2.20 to 4.06) |
| EQ-5D-5L VAS | −0.37 (−4.03 to 3.28) |
| TTD HR (95% CI)b (Pembro + Ola vs Pembro + Chemo) | |
| QLQ-C30 GHS/QoL | 1.78 (1.16–2.71) |
| QLQ-C30 physical functioning | 1.01 (0.61–1.69) |
| QLQ-C30 emotional functioning | 1.08 (0.69–1.71) |
| QLQ-BR23 systemic therapy side effects | 1.76 (0.88–3.53) |
aBased on a constrained longitudinal data analysis model (cLDA).bBased on stratified Cox regression model.
Conclusions
In pts with metastatic TNBC, stopping chemo in pts with responding or stable disease and treating with maintenance pembro + ola showed similar PRO results when compared with pts who continue pembro + chemo.
Clinical trial identification
NCT04191135.
Editorial acknowledgement
Medical writing assistance was provided by Christabel Wilson, MSc, of ICON plc (Blue Bell, PA, USA).
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Funding for this research was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
Llombart Cussac: Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisor: Genentech-Roche, AstraZeneca, Daiichi Sankyo, Ely Lilly, MSD, GSK, Novartis, Gilead, Menarini, Agendia, Pfizer, and Guardant health.; Financial Interests, Personal and Institutional, Other, Honoraria: Roche, Novartis, Pfizer, Ely Lilly, MSD, Daiichi Sankyo, and AstraZeneca; Financial Interests, Institutional, Other, Institutional research funding: Roche, AstraZeneca, Eisai, Guardant health, MSD, Pfizer, and Agendia.; Financial Interests, Personal and Institutional, Other, Travel/Accommodation/Expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, and Gilead.; Financial Interests, Personal, Other, Patent: (US 2019/ 0338368 A1) HER2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Aleix Prat, Antonio Llombart, Javier Cortés. H.S. Rugo: Financial Interests, Institutional, Other, Institutional Research Support: AstraZeneca, Daiichi Sankyo, F. Hoffmann-La Roche AG/Genentech, Gilead Sciences, GSK, Lilly, Merck & Co., Inc., Rahway, NJ, USA, Novartis Pharmaceuticals, OBI Pharma, Pfizer, Pionyr Immunotherapeutics, and Sermonix Pharmaceuticals.; Financial Interests, Personal and Institutional, Advisory Role, Consultancy/Advisory: Puma, NAPO, Blueprint, and Daiichi Sankyo. M.E. Robson: Financial Interests, Institutional, Other, Institutional Research Support: Artios, AstraZeneca, and Merck.; Financial Interests, Personal and Institutional, Other transfers of value: AstraZeneca, Merck, and Novartis. S. Im: Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Daiichi Sankyo, GSK, Hanmi, Idience, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), Novartis, Pfizer, Bertis, and Roche.; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Boryung Pharm, Daewoong Pharm, Daiichi Sankyo, Eisai, Pfizer, and Roche. F. Dalenc: Financial Interests, Institutional, Advisory Board: Novartis, MSD, DAICHI SANKO, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, Gilead, Novartis; Non-Financial Interests, Advisory Role: AstraZeneca.
J. M. Walshe: Non-Financial Interests, Personal and Institutional, Advisory Role: Daiichi Sankyo; Financial Interests, Personal and Institutional, Advisory Role: Gilead, Lilly, Merck, Novartis. N. Llinas: Financial Interests, Personal and Institutional, Advisory Board: MSD, BMS, Biotoscana, Roche, Pfizer, Eli Lilly, Novartis, and Knight Therapeutics. S. Saji: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Kyowa Kirin, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda.; Financial Interests, Institutional, Other, Institutional funding as local PI: AstraZeneca, Chugai, Daiichi Sankyo, MSD, and Sanofi.; Financial Interests, Institutional, Other, Institutional research grant: Chugai, Daiichi Sankyo, and Taiho.; Financial Interests, Personal and Institutional, Member of Board of Directors: Breast International Group, Japan Breast Cancer Research Group, Japanese Breast Cancer Society, and Japanese Society of Medical Oncology. A. Bardia: Financial Interests, Institutional, Advisory Board, Consultant/Advisory Board: Pfizer, Novartis, Genentech, Merck & Co., Inc., Rahway, NJ, USA, Radius Health, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lilly, andFoundation Medicine.; Financial Interests, Institutional, Other, Contracted Research/Grant (institution): Genentech, Novartis, Pfizer, Merck & Co., Inc., Rahway, NJ, USA, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, and Eli Lilly. N. Harbeck: Financial Interests, Personal, Invited Speaker, Stock and Other Ownership Interests: West German Study Group.; Financial Interests, Personal and Institutional, Other, Honoraria: Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Seagen, Viatris, and Zuelligpharma.; Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role: Gilead, Roche, Sandoz, and Seagen.; Financial Interests, Institutional, Other, Research Funding (institution): Lilly, Novartis, Pfizer, Roche/Genentech, and MSD. A. Haiderali: Financial Interests, Personal, Stocks/Shares, Shareholder / Stockholder / Stock Options: Merck & Co., Inc., Rahway, NJ, USA.; Financial Interests, Personal, Full or part-time Employment, Full-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. L. Fan: Financial Interests, Personal, Full or part-time Employment, Full-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. A.M. Nguyen: Financial Interests, Personal, Stocks/Shares, Shareholder / Stockholder / Stock Options: Merck & Co., Inc., Rahway, NJ, USA.; Financial Interests, Personal, Full or part-time Employment, • Full-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. J.A. Mejia: Financial Interests, Personal, Stocks/Shares, Shareholder / Stockholder / Stock Options: Merck & Co., Inc., Rahway, NJ, USA.; Financial Interests, Personal, Full or part-time Employment, Full-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. D.W. Cescon: Financial Interests, Personal and Institutional, Advisory Role, Consultancy/Advisory: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, GSK, Inflex, Inivata/NeoGenomics, Lilly, Merck, Novartis, Pfizer, Roche, and Saga; Financial Interests, Institutional, Other, Research Support (institution): AstraZeneca, Guardant Health, Gilead, GSK, Inivata/NeoGenomics, Knight, Merck, Pfizer, ProteinQure, and Roche; Financial Interests, Personal, Other, 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. All other authors have declared no conflicts of interest.