ESMO 2021: Pembrolizumab Versus Placebo as Adjuvant Therapy for Patients with RCC: Patient-Reported Outcomes in KEYNOTE-564

( The European Society of Medical Oncology (ESMO) 2021 annual meeting’s non-prostate cancer proffered paper session included a presentation by Dr. Toni Choueiri discussing patient-reported outcomes (PROs) among patients in KEYNOTE-564 receiving pembrolizumab versus placebo as adjuvant therapy for renal cell carcinoma (RCC). Nephrectomy is the standard of care treatment for locoregional RCC, but nearly half of patients may eventually experience disease recurrence after surgery. Currently, there is no globally accepted standard adjuvant therapy supported by high levels of evidence.

The randomized, double-blind, phase III KEYNOTE-564 (NCT03142334) study met its primary endpoint of disease-free survival with adjuvant pembrolizumab vs placebo (HR 0.68, 95% CI 0.53-0.87) following surgery in patients with RCC.1 PROs provide an understanding of participant experiences in oncology trials that can complement traditional clinical metrics of efficacy and safety. At the ESMO 2021 congress, Dr. Choueiri and colleagues presented PRO findings for adjuvant pembrolizumab versus placebo in KEYNOTE-564.

PROs were evaluated in all randomized patients 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. A summary of the PRO assessment schedule and instruments is as follows:


Prespecified secondary endpoints included least square 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 scales from baseline to week 52. As an exploratory analysis, the overall summary of the proportion of patients with improved/stable/deteriorated symptom scores and health-related quality of life was assessed.

As of December 14, 2020, no patients remained on treatment, and median (range) time from randomization to data cutoff date was 24.1 (14.9-41.5) months. Among 496 patients randomized to pembrolizumab and 498 patients to placebo, >90% completed the FSKI-DRS and QLQC30 at baseline and >60% completed each instrument at week 52. Least square mean change in FKSI-DRS score was −1.12 (95% CI, −1.53-−0.71) with pembrolizumab vs −0.45 (95% CI, −0.84-−0.05) with placebo, both of which were below the threshold of ≥3 for clinically meaningful change in FKSI-DRS:


Least square mean change in QLQ-C30 GHS/QoL score was −4.25 (95% CI, −6.32-−2.19) with pembrolizumab vs −1.68 (95% CI, −3.69-0.32) with placebo. Additionally, least square mean change in QLQ-C30 physical function score was −1.81 (95% CI, −3.19-−0.43) with pembrolizumab 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


Dr. Choueiri concluded his presentation of PROs in the KEYNOTE-564 trial with the following take-home messages:

  • KEYNOTE-564 is the first positive phase 3 study of adjuvant immunotherapy in RCC
  • No clinically meaningful changes from baseline in health-related QoL or symptom scores were observed with adjuvant pembrolizumab or placebo. These scores remained stable over time
  • PRO findings suggested that adjuvant pembrolizumab was tolerable from a patient perspective
  • Pembrolizumab is a potential new standard of care for patients with RCC in the adjuvant setting


Presented by: Toni K. Choueiri, MD, Jerome and Nancy Kohlberg Professor of Medicine, Harvard Medical School, Attending Physician, Solid Tumor Oncology, Dana-Farber Cancer Institute, Director, Genitourinary (GU) Oncology Disease, Center, Dana-Farber Cancer Institute, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.


  1. Choueiri TK, Tomczak P, Park SH, et al. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021 Aug 19;385(8):683-694.