200O - Pembrolizumab plus axitinib (pembro + axi) vs sunitinib in metastatic renal cell carcinoma (mRCC) outcomes of the KEYNOTE-426 study in patients from eastern Asia

Background

At the first preplanned interim analysis (median follow-up [defined as time from randomization to data cutoff], 14.2 mo) of the randomized phase III KEYNOTE-426 trial (NCT02853331), first-line pembro + axi vs sunitinib significantly prolonged OS, PFS, and ORR in patients (pts) with mRCC, resulting in pembro + axi becoming a standard of care. After a median 30.6 mo of follow-up, pembro + axi showed continued superior efficacy to sunitinib. Outcomes are presented in pts from KEYNOTE-426 who were enrolled from Eastern Asia.

Methods

Pts with clear cell mRCC and Karnofsky Performance Status score ≥70% were randomly assigned 1:1 to receive pembro 200 mg IV Q3W (maximum 35 cycles) + axi 5 mg PO BID or sunitinib 50 mg PO QD (4 wk on/2 wk off) until disease progression, unacceptable toxicity, death, or study withdrawal. Primary end points were OS and PFS (RECIST v1.1). Secondary end points were ORR and safety.

Results

Of 130 pts enrolled in Eastern Asia (pembro + axi: 62, sunitinib: 68), 44 (71.0%) and 58 (86.6%) treated with pembro + axi and sunitinib, respectively, discontinued. Median follow-up was 29.8 mo (range, 24.6-37.7) for pembro + axi and 29.9 mo (24.6-37.9) for sunitinib. Median OS (95% CI) was not reached in the pembro + axi and sunitinib groups (HR, 0.71; 95% CI, 0.38-1.31; 24-mo rate, 77.4% and 67.6%, respectively). Median PFS (95%CI) was 18.0 mo (12.5-23.5) with pembro + axi and 10.0 mo (7.1-15.0) with sunitinib (HR, 0.59; 95% CI, 0.37-0.93; 24-mo rate, 33.7% and 18.7%, respectively). ORR was 64.5% with pembro + axi and 44.1% with sunitinib; 14.5% and 5.9% of patients in the respective groups exhibited CR. Five (8.1%) and 33 (48.5%) pts in the pembro + axi and sunitinib groups, respectively, received a PD-1/PD-L1 inhibitor as subsequent therapy; 28 (45.2%) and 36 (52.9%), respectively, received a subsequent VEGF/VEGFR inhibitor. Grade 3-5 treatment-related adverse events occurred in 43 (69.4%) and 50 (74.6%) pts in the pembro + axi and sunitinib groups, respectively.

Conclusions

In KEYNOTE-426, in pts who enrolled in East Asia, treatment benefit and tolerability profile of pembro + axi compared to sunitinib were similar to what was observed in the global study population.

Clinical trial identification

NCT02853331; August 2, 2016.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

S. Tamada: Speaker Bureau/Expert testimony: MSD. G. Kimura: Honoraria (self): Ono, BMS, Novartis, Pfizer, Bayer, Chugai, MSD; Research grant/Funding (institution): Ono/BMS, Bayer, Chugai, MSD, Astellas, AstraZeneca, Taiho. J. Lin, R. Perini: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. L.R. Molife: Shareholder/Stockholder/Stock options, Full/Part-time employment: MSD. T.B. Powles: Honoraria (self): BMS, Seattle Genetics, Ipsen, Merck, MSD, Novartis, Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca, Roche; Advisory/Consultancy: AstraZeneca, BMS, Exelexis, Incyte, Ipsen, Merck/MSD, Novartis, Pfizer, Seattle Genetics. B. Rini: Advisory/Consultancy: Merck, Roche, Pfizer, AVEO, BMS, Arravive, 3D Medicines, Synthorx, Surface Oncology, Alkermes; Shareholder/Stockholder/Stock options: PTC Therapeutics; Travel/Accommodation/Expenses: Merck, BMS, Pfizer; Research grant/Funding (institution): Merck, Roche, Pfizer, AVEO, BMS, AstraZeneca. All other authors have declared no conflicts of interest.