Background
The randomized, double-blind, phase III KEYNOTE-564 (NCT03142334) study met its primary endpoint of disease-free survival with adjuvant pembro vs placebo following surgery in pts with RCC. We present PRO findings for adjuvant pembro vs placebo in KEYNOTE-564.
Methods
PRO were evaluated in all randomized pts with ≥1 dose study treatment and ≥1 completed assessment for the specific outcome. FKSI-DRS and EORTC QLQ-C30 were administered electronically at cycles 1, 5, 9, 13, and 17, treatment discontinuation, 30 days after last dose, and annually thereafter until recurrence or new therapy. Prespecified secondary endpoints included least square (LS) mean change in symptom scores as measured by FKSI-DRS and health-related quality of life as measured by the QLQ-C30 global health status/quality of life (GHS/QoL) and physical functioning (PF) scales from baseline to week 52. CIs were nominal and descriptive.
Results
As of Dec 14, 2020, no pts remained on treatment and median (range) time from randomization to data cutoff date was 24.1 (14.9-41.5) months. Among 496 pts randomized to pembro and 498 pts to placebo, >90% completed the FSKI-DRS and QLQ-C30 at baseline and >60% completed each instrument at week 52. LS mean change in FKSI-DRS score was −1.12 (95% CI, −1.53-−0.71) with pembro vs −0.45 (95% CI, −0.84-−0.05) with placebo; both were below the threshold of ≥3 for clinically meaningful change in FKSI-DRS. LS mean change in QLQ-C30 GHS/QoL score was −4.25 (95% CI, −6.32-−2.19) with pembro vs −1.68 (95% CI, −3.69-0.32) with placebo. LS mean change in QLQ-C30 PF score was −1.81 (95% CI, −3.19-−0.43) with pembro vs −0.90 (95% CI, −2.23-0.44) with placebo. Mean score change for both arms in both scales was below the clinically meaningful change threshold of ≥10 for QLQ-C30. Health-related QoL and symptom scores were maintained across all evaluated time points.
Conclusions
No clinically meaningful changes from baseline in health-related QoL or symptom scores were observed with adjuvant pembro or placebo. These scores remained stable over time. PRO findings suggested that adjuvant pembro was tolerable from a pt perspective.
Clinical trial identification
NCT03142334.
Editorial acknowledgement
Medical writing assistance was provided by Ina Nikolaeva 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
T.K. Choueiri: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal and Institutional, Research Grant: BMS; Other, Personal, Other, manuscript preparation, travel/lodging: BMS; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal and Institutional, Research Grant: Exelixis; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Exelixis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: AstraZeneca; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal and Institutional, Research Grant: Lilly; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Lilly; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal and Institutional, Research Grant: Eisai; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Eisai; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Novartis; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Research Grant: GSK; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: GSK; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Pfizer; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal and Institutional, Research Grant: EMD Serono; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: EMD Serono; Financial Interests, Personal, Stocks/Shares: Pionyr; Financial Interests, Personal, Stocks/Shares: Tempest; Financial Interests, Institutional, Funding: Dana-Farber Cancer Institute; Non-Financial Interests, Personal, Invited Speaker: NCCN kidney panel; Non-Financial Interests, Personal, Invited Speaker: NCI Steering Committee. P. Tomczak: Financial Interests, Institutional, Funding: MSD. S.H. Park: Financial Interests, Institutional, Funding: MSD. B. Venugopal: Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: EUSA Pharma; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Merck Serono. S. Symeonides: Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Verastem; Financial Interests, Personal and Institutional, Advisory Role: Bicycle Therapeutics; Financial Interests, Personal and Institutional, Advisory Role: Ellipses; Financial Interests, Personal and Institutional, Advisory Role: Medannex; Financial Interests, Personal and Institutional, Advisory Role: Vaccitech; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: EUSA; Financial Interests, Personal and Institutional, Advisory Board: EUSA; Financial Interests, Personal and Institutional, Advisory Board: Eisai; Financial Interests, Personal and Institutional, Advisory Board: Merck Serono; Financial Interests, Personal and Institutional, Advisory Board: Pfizer; Non-Financial Interests, Personal, Other, travel: Ipsen. J. Hajek: Financial Interests, Institutional, Funding: MSD. T. Ferguson: Financial Interests, Institutional, Funding: MSD. Y. Chang: Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Janssen. J.L. Lee: Financial Interests, Personal, Advisory Board: Pfizer Korea; Financial Interests, Personal, Advisory Board: Ipsen Korea; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Role: Novartis Korea; Financial Interests, Personal, Advisory Board: Astellas Korea; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Stocks/Shares: Myovant Science; Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: SeaGen; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. N. Haas: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Aveo; Financial Interests, Personal, Advisory Role: Roche. P. Sawrycki: Financial Interests, Personal, Advisory Role: MSD. N. Sarwar: Financial Interests, Institutional, Funding: MSD. M. Gross-Goupil: Financial Interests, Institutional, Funding: MSD; Financial Interests, Personal, Other, honoraria, travel: Amgen; Financial Interests, Personal, Other, honoraria, travel: Astellas; Financial Interests, Personal, Other, honoraria, travel: AstraZeneca; Financial Interests, Personal, Other, honoraria, travel: Bayer; Financial Interests, Personal, Other, honoraria, travel: BMS; Financial Interests, Personal, Other, honoraria, travel: Ipsen; Financial Interests, Personal, Other, honoraria, travel: Janssen; Financial Interests, Personal, Other, honoraria, travel: Merck KGaA; Financial Interests, Personal, Other, honoraria, travel: MSD; Financial Interests, Personal, Other, honoraria, travel: Novartis; Financial Interests, Personal, Other, honoraria, travel: Pfizer; Financial Interests, Personal, Other, honoraria, travel: Roche; Financial Interests, Personal, Other, honoraria, travel: Sanofi. A. Thiery-Vuillemin: Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, honoraria, travel/lodging: Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, honoraria, travel/lodging: AstraZeneca; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Other, honoraria: Sanofi; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Other, honoraria, travel/lodging: Janssen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Other, honoraria: Novartis; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Other, honoraria, travel/lodging: Ipsen; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Other, honoraria: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Other, honoraria, travel/lodging: MSD; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Other, honoraria, travel/lodging: Roche/Genentech; Financial Interests, Personal, Other, honoraria, travel/lodging: Astellas Pharma. M. Mahave: Financial Interests, Institutional, Funding: MSD. T.L. Saretsky: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. P. Zhang: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. J. Willemann-Rogerio: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. D.I. Quinn: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Other, data safety: Eisai; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Bayer. T.B. Powles: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Johnson & Johnson; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Johnson & Johnson; Financial Interests, Institutional, Research Grant: Eisai.