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ASCO GU 2019

ASCO GU 2019: First-line Pembrolizumab Monotherapy for Advanced Non-Clear Cell Renal Cell Carcinoma: Results from KEYNOTE-427 Cohort B

San Francisco, CA (UroToday.com) As most renal cell carcinomas are a clear cell in origin, data directing treatment in the non-clear cell realm are limited.  Often, a patient with non-clear cell histologies is excluded from clinical trials.  Current treatment guidelines for patients with advanced renal cell carcinoma and non-clear cell histologies are to enroll in a clinical trial or consider utilization of a VEGF inhibitor (sunitinib).  PD-1/PD-L1 checkpoint inhibition (nivolimab + ipilimumab) was approved for patients with intermediate or poor risk previously untreated advanced RCC.  Cohort A of KEYNOTE 427 demonstrates single agent pembrolizumab had promising antitumor activity as first line therapy for clear cell RCC.

In this presentation, Dr. McDermott discussed the Cohort B of the KEYNOTE 427 trial, where patients with recurrent, advanced, or metastatic non-clear cell RCC (n=165) and no prior systemic therapy were given pembrolizumab 200mg Q 3 weeks.  Endpoints included objective response rates, duration of response, progression-free survival, overall response, safety and tolerability. 

At a cutoff date of September 2018, median follow up in this cohort was 11.1 months.  110 patients discontinued treatment, primarily due to progressive disease (76/110) and clinical progression (16/110).  Only 10 patients discontinued treatment due to adverse events.  71% of patients had papillary RCC, 13% chromophobe and 16% unclassified.  68% of patients were in the intermediate or poor risk group and 62% PD-L1 positive. 

A blinded independent central review demonstrated an objective response rate of 25% for papillary, 9.5% chromophobe, and 35% for unclassified renal cell carcinomas.  Furthermore, approximately 55% of patients experienced a reduction in tumor burden.  Median time to response was 2.8 months.  Favorable IMDC risk group had a 28% objective response rate compared to 23% for intermediate and poor risk.  Stratified by PD-L1 expression, demonstrated a 33% objective response for PD-L1 positive compared to 10% for PD-L1 negative tumors.  65% of patients had any grade adverse events, and 18% high grade.  Discontinuation due to treatment-related adverse events were reported in 6% of patients.

In summary, Keynote 427 Cohort B results demonstrate promising anti-tumor activity with first line pembrolizumab monotherapy in non-clear cell advanced RCC.  The safety profile was similar to other previously reported trials with pembrolizumab monotherapy.  These results support further trials with PD-1/PD-L1 inhibition in non-clear cell RCCs. 

Presented by: David F. McDermott, MD, Dana Farber Cancer Center, Boston, Massachusetts

Written by: David B. Cahn, DO, MBS, @dbcahn, Fox Chase Cancer Center at the Annual ASCO GU meeting 2019, San Francisco, CA, Twitter: @shekabhishek at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

Further Related Content:
KEYNOTE-427 Cohort A: Pembrolizumab Monotherapy as First-line Therapy in advanced clear cell Renal Cell Carcinoma (ccRCC)