1782MO - Health-related quality of life (HRQoL) in KEYNOTE-604: Pembrolizumab (pembro) or placebo added to etoposide and platinum (EP) as first-line therapy for ES-SCLC

Background

In the randomized, double-blind, phase 3 KEYNOTE-604 study (NCT03066778), pembro-EP significantly improved PFS and had no unexpected toxicities vs placebo-EP as first-line therapy for ES-SCLC; the HR for OS favored pembro-EP, but the significance threshold was missed. We present patient-reported outcomes (PROs) from KEYNOTE-604.

Methods

453 patients (pts) were randomized 1:1 to pembro 200 mg Q3W or saline placebo for ≤35 cycles plus 4 cycles of standard-dose EP. PRO questionnaires, including the EORTC QLQ-C30 and QLQ-LC13, were administered electronically before other trial-related procedures at cycles 1-9, 11, 13, 15, and 17, treatment discontinuation, and the 30-day safety follow-up. Mean change from baseline to wk 18 in the QLQ-C30 global health status (GHS)/QoL scale and time to true deterioration (TTD) in the QLQ-C30/LC13 composite of cough, chest pain, or dyspnea were secondary study end points; TTD in the QLQ-C30 GHS/QoL scale was a protocol-specified exploratory end point. TTD was defined as time to first ≥10-point worsening from baseline with confirmation under a right-censoring rule. HRQoL was assessed in all treated pts who completed ≥1 PRO assessment (N = 439). P values are nominal and two-sided.

Results

PRO compliance was ≥89% in both arms at baseline and wk 18. Mean QLQ-C30 GHS/QoL scale score was 60.54 in the pembro-EP arm and 58.37 in the placebo-EP arm at baseline. Score improved in both arms at wk 18; the least squares mean change from baseline (95% CI) was 8.66 points (5.26-12.06) in the pembro-EP arm and 4.23 points (0.93-7.52) in the placebo-EP arm for a difference in least squares means of 4.43 points (95% CI 0.21-8.66; P = .040). Median TTD in the QLQ-C30/LC13 composite of cough, chest pain, or dyspnea was not reached (NR) for pembro-EP and was 8.7 mo for placebo-EP (HR 0.80 [95% CI 0.56-1.14]; P = .208). Median TTD in the QLQ-C30 GHS/QoL scale was NR in either arm (HR 0.78 [95% CI 0.52-1.18]; P = .238).

Conclusions

Adding pembro to EP did not decrease, and may improve, HRQoL compared with placebo-EP as first-line therapy for ES-SCLC. Along with the efficacy and safety data observed in KEYNOTE-604, PRO data support the benefit of pembro in SCLC.

Clinical trial identification

NCT03066778, originally posted on February 28, 2017.

Editorial acknowledgement

Melanie Leiby of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

H.R. Kim: Honoraria (self), Speaker Bureau/Expert testimony: Ono; Honoraria (self), Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD. M.M. Awad: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Achilles Therapeutics; Advisory/Consultancy: ARIAD; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Gristone Oncology; Advisory/Consultancy: Hengrui Therapeutics; Advisory/Consultancy: Maverick Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Advisory/Consultancy: Nektar; Advisory/Consultancy: Neon Therapeutics; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Syndax; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Lilly. A. Navarro: Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony: Oryzon Genomics; Research grant/Funding (institution): MSD. M. Gottfried: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca. S. Peters: Honoraria (institution), Advisory/Consultancy: AbbVie; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Biocartis; Honoraria (institution), Advisory/Consultancy: Bioinvent; Honoraria (institution), Advisory/Consultancy: Blueprint Medicines; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Clovis; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy: Debiopharm; Honoraria (institution), Advisory/Consultancy: Eli Lilly; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): F. Hoffmann-La Roche; Honoraria (institution), Advisory/Consultancy: Foundation Medicine; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Illumina; Honoraria (institution), Advisory/Consultancy: Janssen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Honoraria (institution), Advisory/Consultancy: Merrimack; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (institution), Advisory/Consultancy: Pharma Mar; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (institution), Advisory/Consultancy: Regeneron; Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics; Honoraria (institution), Advisory/Consultancy: Takeda; Honoraria (institution), Advisory/Consultancy: Vaccibody; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Biodesix. T. Csőszi: Advisory/Consultancy: Novartis pharma SAS; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): MSD. P.K. Cheema: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Hoffman la Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Takeda; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Genomic Health. D. Rodriguez-Abreu: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. M. Wollner: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Novartis. J.C-H. Yang: Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Eli Lilly; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (institution), Advisory/Consultancy: Merck Serono; Honoraria (institution), Advisory/Consultancy: Celgene; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: Yuhan; Honoraria (institution), Advisory/Consultancy: Hansoh; Honoraria (institution), Advisory/Consultancy: Blueprint Medicines; Honoraria (institution), Advisory/Consultancy: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Takeda; Honoraria (institution), Advisory/Consultancy: Incyte; Advisory/Consultancy: Roche. J. Mazieres: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Lilly/ImClone; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Roche/Genentech; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche. F.J. Orlandi: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche/Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Sanofi; Speaker Bureau/Expert testimony: AstraZeneca/Genentech; Research grant/Funding (self): AstraZeneca/MedImmune; Speaker Bureau/Expert testimony: Roche; Research grant/Funding (self): Amgen; Research grant/Funding (self): Astellas Medivation; Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Celltrion; Research grant/Funding (self): mAbxience; Research grant/Funding (self): Nektar. A. Luft: Research grant/Funding (institution): MSD. M. Gümüş: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (institution): Novartis; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution), Research grant/Funding (institution): MSD; Honoraria (institution): Amgen; Honoraria (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Gen İlac; Advisory/Consultancy: Astellas. T. Kato: Research grant/Funding (institution): MSD. G.P. Kalemkerian: Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Y. Luo, M.L. Santorelli, M.C. Pietanza: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp. C.M. Rudin: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Amgen; Advisory/Consultancy: Ascentage Pharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Celgene; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Harpoon Therapeutics; Advisory/Consultancy: Loxo; Advisory/Consultancy: PharmaMar; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Viralytics; Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Advisory/Consultancy: Bicycle Therapeutics; Advisory/Consultancy: Bridge Medicines; Advisory/Consultancy: Ipsen; Research grant/Funding (institution): AbbVie/Stemcentrx.