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Randomized Controlled Trial
. 2024 Feb 2;29(2):142-150.
doi: 10.1093/oncolo/oyad231.

Patient-Reported Outcomes in KEYNOTE-564: Adjuvant Pembrolizumab Versus Placebo for Renal Cell Carcinoma

Toni K Choueiri  1 , Piotr Tomczak  2 , Se Hoon Park  3 , Balaji Venugopal  4 , Stefan Symeonides  5 , Jaroslav Hajek  6 , Thomas Ferguson  7 , Yen-Hwa Chang  8 , Jae Lyun Lee  9 , Naomi Haas  10 , Piotr Sawrycki  11 , Naveed Sarwar  12 , Marine Gross-Goupil  13 , Antoine Thiery-Vuillemin  14 , Mauricio Mahave  15 , Go Kimura  16 , Rodolfo F Perini  17 , Todd L Saretsky  17 , Rituparna Bhattacharya  17 , Lei Xu  17 , Thomas Powles  18
Affiliations
Randomized Controlled Trial

Patient-Reported Outcomes in KEYNOTE-564: Adjuvant Pembrolizumab Versus Placebo for Renal Cell Carcinoma

Toni K Choueiri et al. Oncologist. .

Abstract

Background: In patients with renal cell carcinoma (RCC) enrolled in the phase III KEYNOTE-564 trial (NCT03142334), disease-free survival (DFS) following nephrectomy was prolonged with use of adjuvant pembrolizumab therapy versus placebo. Patient-reported outcomes (PROs) provide an important measure of health-related quality of life (HRQoL) and can complement efficacy and safety results.

Patients and methods: In KEYNOTE-564, 994 patients were randomly assigned to receive pembrolizumab 200 mg (n = 496) or placebo (n = 498) intravenously every 3 weeks for ≤17 cycles. Patients who received ≥1 dose of treatment and completed ≥1 HRQoL assessment were included in this analysis. HRQoL end points were assessed using the EORTC QLQ-C30, FKSI-DRS, and EQ VAS. Prespecified and exploratory PRO end points were mean change from baseline in EORTC QLQ-C30 GHS/QoL score, EORTC QLQ-C30 physical function subscale score, and FKSI-DRS score.

Results: No clinically meaningful difference in least squares mean scores for pembrolizumab versus placebo were observed at week 52 for EORTC QLQ-C30 GHS/QoL (-2.5; 95% CI -5.2 to 0.1), EORTC QLQ-C30 physical functioning (-0.87; 95% CI -2.7 to 1.0), and FKSI-DRS (-0.7; 95% CI -1.2 to -0.1). Most PRO scores remained stable or improved for the EORTC QLQ-C30 GHS/QoL (pembrolizumab, 54.3%; placebo, 67.5%), EORTC QLQ-C30 physical functioning (pembrolizumab, 64.7%; placebo, 68.8%), and FKSI-DRS (pembrolizumab, 58.2%; placebo, 66.3%).

Conclusions: Adjuvant treatment with pembrolizumab did not result in deterioration of HRQoL. These findings together with the safety and efficacy findings support adjuvant pembrolizumab treatment following nephrectomy.

Trial registration: Clinicaltrials.gov Identifier: NCT03142334.

Keywords: health-related quality of life; nephrectomy; pembrolizumab; renal cell carcinoma.

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Conflict of interest statement

Toni K. Choueiri reported institutional and personal paid and unpaid support for research, advisory boards, consultancy, and honoraria from: AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVIA, Infinity Pharmaceuticals, Ipsen, Janssen, Kanaph Therapeutics, Lilly, Merck, Nikang, Precede Bio, Novartis, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest Therapeutics, UpToDate, and CME events (PeerView, OncLive, Michael J. Hennessy Associates, and others) outside the submitted work; intellectual property: Molecular mutations and immunotherapy response and circulating tumor DNA; ownership interest: Tempest Therapeutics, Pionyr, Osel, Precede Bio; Scientific Advisory Boards: National Comprehensive Cancer Network, Genitourinary Steering Committee, American Society of Clinical Oncology/European Society for Medical Oncology, ACCRU, KidneyCAN; and has mentored several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components; T.K.C. is supported in part by research funding from the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. Piotr Tomczak has received research funding from Merck Sharp & Dohme Oncology. Balaji Venugopal has received honoraria from Bristol Myers Squibb, Eisai, EUSA Pharma, and Ipsen. Stefan Symeonides has received research funding from MSD and Verastem, honoraria from Eisai BioNTech, EUSA, Ipsen, and MSD, has consulting/advisory relationships with Bristol Myers Squibb, Boxer Capital, Duke Street Bio, Eisai, Ellipses, EUSA, Medannex, Merck Serono, Merck Sharp and Dohme, Pfizer, and Vaccitech, and serves on the scientific advisory board for Cancer Drug Development Forum. Thomas Ferguson has consulting/advisory relationships with Merck Sharp and Dohme, Bristol Myers Squibb, and Pfizer. Jae Lyun Lee has received research funding from Pfizer, Ipsen, Bristol Myers Squibb, Merck Sharp and Dohme, Merck, Roche, AstraZeneca, and Seagen, serves on the scientific advisory board for Pfizer Korea, Astella Korea, Bristol Myers Squibb, Merck, Merck Sharp and Dohme, and AstraZeneca, and has ownership interests in Amgen, Johnson and Johnson, Merck, Beigene, and Innovent. Naomi Haas serves on the scientific advisory board for Aveo, Merck, Eisai, Bristol Myers Squibb, Exelixis, and Roche. Marine Gross-Goupil serves on the scientific advisory board and received honoraria from Bristol Myers Squibb, AstraZeneca, Merck Sharp and Dohme, Ipsen, Eisai, Pfizer, Roche, and Novartis, and has a consulting/advisory relationship with Bristol Myers Squibb, AstraZeneca, Merck Sharp and Dohme, Ipsen, Eisai, and Pfizer. Antoine Thiery-Vuillemin receives research funding from Merck Sharp and Dohme, Pfizer, Ipsen, and Bayer, has consulting/advisory relationship with Roche, Merck Sharp and Dohme, Johnson & Johnson, Bristol Myers Squibb, Astellas, Ipsen, AstraZeneca, and Novartis, has received honoraria from Roche, Merck Sharp and Dohme, Johnson & Johnson, Bristol Myers Squibb, Astellas, Ipsen, AstraZeneca, and Novartis, and serves on the scientific advisory board for BIONIKK trial and steering committee of French GETUG academic group. Go Kimura has received honoraria from Ono Pharmaceutical Co, Ltd., Bristol Myers Squibb K.K., Bayer Yakuhin Ltd., Merck Biopharma, Chugai Pharmaceutical Co Ltd., MSD K.K., Eisai Co., Ltd., Takeda Pharmaceutical Company Limited, and Sanofi K.K. Rodolfo F. Perini is an employee of and has ownership interests in Merck & Co., Inc., Rahway, NJ, USA. Todd L. Saretsky is an employee of and has ownership interests in Merck & Co., Inc., Rahway, NJ, USA. Rituparna Bhattacharya is an employee of and has ownership interests in Merck & Co., Inc., Rahway, NJ, USA. Lei Xu is an employee of and has ownership interests in Merck & Co., Inc., Rahway, NJ, USA. Thomas Powles receives research funding from Astellas, Open Health, AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, Merck, Merck Sharp and Dohme, Novartis, Pfizer, Seattle Genetics, Merck Serono, Johnson & Johnson, and Eisai; has consulting/advisory relationships with AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Merck, Merck Sharp and Dohme, Novartis, Pfizer, Seagen, Merck Serono, Astellas, Johnson & Johnson, Eisai, and Mashup Ltd.; and has received honoraria from Roche, Pfizer, Merck Sharp and Dohme, AstraZeneca, and Ipsen. The other authors indicated no financial relationships.

Figures

Figure 1.
Figure 1.
Trial profile.
Figure 2.
Figure 2.
LSM change from baseline to week 52 in EORTC QLQ-C30 global health status/quality-of-life (A) functioning scales and (B) symptom scales. EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; LSM, least-squares mean; QoL, quality of life.
Figure 3.
Figure 3.
Proportion of patients with improved, stable, and deteriorated EORTC QLQ-C30 and FKSI-DRS scoresa. an = 60 in the pembrolizumab group and n = 53 in the placebo group had no assessment in the FKSI-DRS; n = 58 in the pembrolizumab group and n = 50 in the placebo group had no assessment in the EORTC QLQ-C30. EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; FKSI-DRS, Functional Assessment of Cancer Therapy–Kidney Symptom Index Disease-Related Symptoms; GHS, global health status; QoL, quality of life.
Figure 4.
Figure 4.
Empirical mean change from baseline to week 104 in (A) EORTC QLQ-C30 GHS/QoL, (B) EORTC QLQ-C30 physical functioning, and (C) FKSI-DRS. CI, confidence interval; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; FKSI-DRS, Functional Assessment of Cancer Therapy–Kidney Symptom Index Disease-Related Symptoms; GHS, global health status; QoL, quality of life.
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