2019 ASCO Annual Meeting!
Session: Genitourinary (Nonprostate) Cancer
Type: Oral Abstract Session
Time: Monday June 3, 8:00 AM to 11:00 AM
Location: Arie Crown Theater
Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC): Outcomes in the combined IMDC intermediate/poor risk and sarcomatoid subgroups of the phase 3 KEYNOTE-426 study.
Genitourinary (Nonprostate) Cancer
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 4500)
Author(s): Brian I. Rini, Elizabeth R. Plimack, Viktor Stus, Rustem Gafanov, Robert Hawkins, Dmitry Nosov, Frederic Pouliot, Denis Soulieres, Bohuslav Melichar, Ihor Vynnychenko, Sergio Jobim Azevedo, Delphine Borchiellini, Raymond S. McDermott, Jens Bedke, Satoshi Tamada, Shuyan Wan, Rodolfo F. Perini, Mei Chen, Michael B. Atkins, Thomas Powles; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Fox Chase Cancer Center, Philadelphia, PA; Dnipropetrovsk Medical Academy of Ministry of Health of Ukraine, Dnipro, Ukraine; Russian Scientific Center of Roentgenoradiology, Moscow, Russian Federation; The Christie NHS Foundation Trust, Manchester, United Kingdom; Central Clinical Hospital with Outpatient Clinic, Moscow, Russian Federation; CHU de Québec and Université Laval, Quebec City, QC, Canada; Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada; Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic; Sumy State University, Sumy Regional Oncology Center, Sumy, Ukraine; Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Centre Antoine Lacassagne, Université Côte d’Azu, Nice, France; Adelaide and Meath Hospital and University College Dublin, Dublin, Ireland; Department of Urology, Eberhard-Karls University Tübingen, Tübingen, Germany; Osaka City University Hospital, Osaka, Japan; Merck & Co., Inc., Kenilworth, NJ; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC; Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
Background: In KEYNOTE-426, pembro + axi significantly improved OS (HR 0.53, P < .0001), PFS (HR 0.69, P = .0001), and ORR (59.3% vs 35.7%, P < .0001) vs sunitinib and had manageable toxicity as first-line therapy for mRCC (NCT02853331). The pembro + axi benefit was observed across all IMDC risk groups and regardless of PD-L1 expression. We present data for the combined intermediate/poor risk group and for patients (pts) with sarcomatoid features. Methods: 861 eligible pts with clear-cell mRCC, no prior systemic therapy for mRCC, and KPS ≥70 were randomized 1:1 to pembro 200 mg IV Q3W for a maximum of 35 cycles plus axi 5 mg orally BID (N = 432) or sunitinib 50 mg orally QD (4-wk on/2-wk off) (N = 429). Primary endpoints were OS and PFS (RECIST v1.1 by blinded, independent central review [BICR]). ORR (RECIST v1.1 by BICR) was the key secondary endpoint. The intermediate/poor risk group was prespecified; the sarcomatoid group was exploratory. HRs and their 95% CIs were calculated with a Cox proportional hazards model. None of the analyses were multiplicity-controlled. Results: 592 (68.8%) of all randomized pts were of IMDC intermediate/poor risk — 294 in the pembro + axi arm, 298 in the sunitinib arm. Pembro + axi improved OS (HR 0.52, 95% CI 0.37-0.74; 12-mo rate 87.3% vs 71.3%), PFS (HR 0.67, 95% CI 0.53-0.85; median 12.6 vs 8.2 mo), and ORR (55.8% [95% CI 49.9-61.5] vs 29.5% [24.4-35.1]) in pts with intermediate/poor risk; CR rates were 4.8% (95% CI 2.6-7.9) vs 0.7% (0.1-2.4). Of the 578 pts with known status, 105 (18.2%) had sarcomatoid features — 51 in the pembro + axi arm, 54 in the sunitinib arm. Pembro + axi improved OS (HR 0.58, 95% CI 0.21-1.59; 12-mo rate 83.4% vs 79.5%), PFS (HR 0.54, 95% CI 0.29-1.00; median not reached vs 8.4 mo), and ORR (58.8% [95% CI 44.2-72.4] vs 31.5% [19.5-45.6]) in pts with sarcomatoid features; CR rates were 11.8% (95% CI 4.4-23.9) vs 0% (0.0-6.6). Conclusions: Pembro + axi provides benefit in the combined population of pts with IMDC intermediate or poor risk and in pts whose tumors had sarcomatoid features. The observed benefits were consistent with those seen in the total population. Clinical trial information: NCT02853331