ESMO 2021: Pembrolizumab Monotherapy As First-Line Therapy in Advanced Non–Clear Cell RCC: Results After a Minimum of 34 Months of Follow-Up From KEYNOTE-427 Cohort B

( The European Society of Medical Oncology (ESMO) 2021 annual meeting’s non-prostate cancer session included a presentation by Dr. Jae-Lyun Lee discussing updated data of pembrolizumab monotherapy among patients with non-clear cell renal cell carcinoma (RCC) from Cohort B of the KEYNOTE-427 trial. Approved therapies for non-clear cell RCC are needed because most clinical trials have focused on the more prevalent clear cell RCC. The open-label, single-arm, phase II KEYNOTE-427 study was designed to investigate the efficacy and safety of monotherapy with pembrolizumab in treatment-naïve patients with either clear-cell RCC (cohort A) or non-clear cell RCC (Cohort B). In cohort B, after >2 years of follow-up, the objective response rate (ORR) was 26.7%, median overall survival (OS) was 28.9 months, and the median duration of response was 29.0 months in the overall population.1 At the 2021 ESMO congress, Dr. Lee and colleagues presented updated efficacy and safety results after a minimum of 34 months of follow-up for patients with non-clear cell RCC (Cohort B).


Patients with histologically confirmed non-clear cell RCC and measurable disease per RECIST v1.1 who had not previously received systemic therapy were given pembrolizumab 200 mg IV every 3 weeks for up to 35 doses or until progressive disease, unacceptable toxicity, or withdrawal of consent. The trial schema for KEYNOTE-427 is as follows:




 The primary end point was ORR per RECIST v.1.1 by blinded independent central review, and the secondary end points were duration of response and PFS per RECIST v1.1 by blinded independent central review, OS, and safety.

 Of 165 patients included in this trial, 118 (71.5%) had papillary histology, 21 (12.7%) had chromophobe histology, and 26 (15.8%) were unclassified. As of February 5, 2021, median duration of therapy was 6.9 months (range, 0.03-29.2), 55 (33.3%) patients received ≥12 months of treatment, and 25 (15.2%) completed pembrolizumab treatment (35 doses). The patient disposition for Cohort B is as follows:




 The median time from enrollment to data cutoff date was 42.9 months (range, 34.1-50.2). ORR was 26.7% (95% CI, 20.1-34.1; 11 complete responses, 33 partial responses). The median duration of response was 29.0 months (95% CI, 9.8-not reached) and an estimated 53.8% of responders remained in response for at least 24 months. The median PFS was 4.2 months (95% CI, 2.9- 5.6):




Median OS was 29.9 months (95% CI, 24.3-37.4):




At 30 months, the PFS rate was 16.9% and the OS rate was 48.4%. Most patients (59.4%) had a reduction in the sum of target lesions, including 16.4% with a ≥80% reduction in the sum of target lesions. ORR (95% CI) was 28.8% (95% CI, 20.8-37.9), 9.5% (95% CI, 1.2-30.4), and 30.8% (95% CI, 14.3-51.8) for patients with papillary, chromophobe, and unclassified histology, respectively. Treatment-related adverse events occurred in 114 (69.1%) of patients and grade 3-5 treatment related adverse events occurred in 28 (17.0%) patients. Two patients died of treatment-related adverse events (pneumonia and cardiac arrest).


Dr. Lee concluded this presentation of update data from Cohort B of the KEYNOTE-427 trial with the following take-home messages:

  • After a minimum of 34 months of follow-up, first-line pembrolizumab monotherapy continued to demonstrate promising antitumor activity as first-line treatment in advanced non-clear cell RCC
  • The safety and tolerability profile was consistent with previously reported results for this cohort and the established safety profile of pembrolizumab monotherapy. No new safety signals were observed
  • Based on the promising data from KEYNOTE-427, the ongoing phase 2 KEYNOTE-B61 study is being conducted to evaluate the safety and efficacy of first-line combination therapy with pembrolizumab + lenvatinib for patients with non-clear cell RCC


Presented by: Jae-Lyun Lee, MD, PhD, Oncology Department, Asan Medical Center - University of Ulsan College of Medicine, Seoul, Republic of Korea

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. McDermott DF, Lee JL, Ziobro M, et al. Open-label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-line Therapy in Patients with Advanced Non-Clear Cell Renal Cell Carcinoma. J Clin Oncol. 2021 Mar 20;39(9):1029-1039.


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