First-line pembrolizumab (pembro) monotherapy for advanced non‒clear cell renal cell carcinoma (nccRCC): updated follow-up for keynote-427 cohort b

C. Suárez ¹,
J. Lee ²,
M. Ziobro ³,
R.A. Gafanov ⁴,
V.B. Matveev ⁵,
F. Donskov ⁶,
F. Pouliot ⁷,
B.Y. Alekseev ⁸,
P.J. Wiechno ⁹,
P. Tomczak ¹⁰,
M.A. Climent ¹¹,
S.J. Shin ¹²,
R. Kloss Silverman ¹³,
R.F. Perini ¹³,
C. Schloss ¹³,
D.F. McDermott ¹⁴,
M.B. Atkins ¹⁵

¹ Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain ² Medical Oncology, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea ³ Klinika Onkologii Klinicznej, Centrum Onkologii-Instytut im. Marii Sklodowskiej, Cracow, Poland ⁴ Urology, Russian Scientific Center of Roentgenoradiology, 117997 Moscow, Russia ⁵ Medical Oncology, N. N. Blokhin Russian Cancer Research Center, 115478 Moscow, Russia ⁶ Oncology, Aarhus University Hospital, 8000 Aarhus, Denmark ⁷ Research Center, CHU de Quebec and Laval University, G1R 3S1 Quebec, Canada ⁸ Oncourology, P. A. Herzen Moscow Oncology Research Institute, Ministry of Health of the Russian Federation, 125284 Moscow, Russia ⁹ Medical Oncology, Maria Sklodowska-Curie Memorial Cancer Center, 00-001 Warsaw, Poland ¹⁰ Chemotherapy, Clinical Hospital No. 1 of the Poznan University of Medical Sciences, 61-878 Poznań, Poland ¹¹ Medical Oncology, Instituto Valenciano de Oncología, 46009 Valencia, Spain ¹² Internal Medicine, Yonsei University College of Medicine, 120-752 Seoul, Korea ¹³ Medical Oncology, Merck & Co., Inc., 07033 Kenilworth, USA ¹⁴ Hematology/oncology, Beth Israel Deaconess Medical Center, 2215 Boston, USA ¹⁵ Oncology, Georgetown Lombardi Comprehensive Cancer Center, 20007 Washington, USA

Abstract

Publication: September 2019

Background

KEYNOTE-427 (NCT02853344) is a single-arm, open-label, phase 2 study of pembro monotherapy in patients (pts) with advanced clear cell RCC (cohort A) and nccRCC (cohort B). Updated cohort B results with additional follow-up are presented.

Methods

165 pts with histologically confirmed nccRCC, no prior systemic therapy, and measurable disease (RECIST v1.1) enrolled. Pts received pembro 200 mg IV Q3W for 35 cycles (∼2 y) or until progressive disease, unacceptable toxicity, or withdrawal. Primary end point: objective response rate (ORR, RECIST v1.1 by blinded independent central review). Additional end points: duration of response (DOR), PFS, OS, data by sarcomatoid differentiation, histology, and PD-L1 expression (combined positive score [CPS] ≥1 for PD-L1+).

Results

Histology by central pathology review: papillary 72% (n = 118), chromophobe 13% (n = 21), unclassified 16% (n = 26); 62% were PD-L1+. Median follow-up: 15.0 mo (range, 0.9-25.4). Overall ORR was 26.1% (95% CI, 19.5-33.5; 10 [6.1%] CR, 33 [20.0%] PR) and median (range) DOR was 15.3 mo (2.8-21.0+). For responders, 57.3% had a response ≥12 mo. 12-mo PFS and OS rates were 24.7% and 73.7%, respectively. ORR (95% CI) was 28.0% (20.1-37.0) in papillary, 9.5% (1.2-30.4) in chromophobe, and 30.8% (14.3-51.8) in unclassified nccRCC; for responders, 55.4%, 50.0%, and 71.4% in the papillary, chromophobe and unclassified groups had a response ≥12 mo. Median (range) DOR was not reached in the unclassified and was 15.3 mo (2.8-21.0+) for the papillary group. ORR (95% CI) was 42.1% (26.3-59.2) for pts with sarcomatoid differentiation (n = 38). ORR (95% CI) in pts with CPS≥1 and CPS<1 was 35.3% (26.1-45.4) and 10.3% (3.9-21.2), respectively. Grade 3-5 treatment-related adverse events (TRAEs) occurred in 14% of pts. 7 pts died of AEs, 2 of TRAEs (pneumonia and cardiac arrest).

Conclusions

Single-agent pembro continued to show encouraging antitumor activity in nccRCC, especially with papillary or unclassified histology and CPS≥1. Safety profile of pembro was as expected.