Among patients with untreated metastatic renal cell carcinoma (RCC) from Eastern Asia, first line treatment with pembrolizumab plus axitinib provided prolonged overall survival (OS) and progression-free survival (PFS), as well as a higher objective response rate (ORR), than treatment with sunitinib. These findings were reported at the ESMO Asia Virtual Congress 2020, held from 20 to 22 November 2020.

Chihiro Kondoh of the Medical Oncology, Toranomon Hospital in Tokyo, Japan, reported findings from patients participating in the randomised phase III KEYNOTE-426 study (NCT02853331) who were enrolled from Eastern Asia (Japan, South Korea, and Taiwan).

KEYNOTE-426 enrolled patients with clear cell metastatic RCC and Karnofsky performance status score ≥70%. Following 1:1 randomisation, patients were treated with pembrolizumab at 200 mg IV every 3 weeks for a maximum of 35 cycles plus oral axitinib at 5 mg twice daily or oral sunitinib at 50 mg daily in a 4 weeks on 2 weeks off cycle until disease progression, unacceptable toxicity, death, or study withdrawal.

Primary endpoints included OS and PFS per RECIST v1.1 and the secondary endpoints were ORR and safety.

Based on data reported from the first pre-planned interim analysis of KEYNOTE-4261, the combination of pembrolizumab and axitinib became a standard of care for patients with untreated advanced or metastatic RCC. With a median follow-up of 14.2 months the combination significantly prolonged OS, PFS, and improved ORR in this patient population. Updated findings after a median 30.6 months of follow-up showed that pembrolizumab plus axitinib continued to demonstrate efficacy that was superior to sunitinib with respect to the same endpoints.2

Fewer patients receiving pembrolizumab/axitinib required subsequent therapy

From 130 patients enrolled in Eastern Asia, 62 were treated with pembrolizumab plus axitinib and 68 received sunitinib. In the Eastern Asian population, 44 (71.0%) patients on the pembrolizumab plus axitinib combination and 58 (86.6%) patients treated with sunitinib discontinued treatment.

With a median follow-up of 29.8 (range, 24.6 to 37.7) months for pembrolizumab plus axitinib and 29.9 (range, 24.6 to 37.9) months for sunitinib in this population, median OS was not reached in either treatment arm (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.38-1.31) and the 24-month OS rates were 77% versus 68%, respectively.


Overall survival in the intent-to-treat population.

© Chihiro Kondoh.

With pembrolizumab plus axitinib median PFS was 18.0 months (95% CI 12.5-23.5) compared to 10.0 months (95% CI 7.1-15.0) with sunitinib (HR 0.59; 95% CI 0.37-0.93). The 24-month PFS rates were 34% and 19%, respectively.

The ORR was 64.5% with pembrolizumab plus axitinib versus 44.1% with sunitinib and 14.5% versus 5.9% of patients achieved complete response.

Subsequent therapy with a PD-1/L1 inhibitor in patients who discontinued treatment was adminstered to 5 (11%) patients on pembrolizumab plus axitinib compared to 33 (57%) patients on sunitinib, and 28 (64%) versus 36 (62%) patients, respectively, received subsequent treatment with a VEGF/VEGFR inhibitor.

Grade 3-5 treatment-related adverse events occurred in 43 (69.4%) patients on pembrolizumab plus axitinib and 50 (74.6%) patients on sunitinib.



Treatment-related adverse events in the study.

© Chihiro Kondoh.


According to the authors, patients enrolled from Eastern Asia in KEYNOTE-426 demonstrated treatment benefit with pembrolizumab plus axitinib compared to sunitinib and tolerability. The findings were consistent with those observed in the global study population and support pembrolizumab plus axitinib as a first line treatment option for RCC in East Asian patients.

The study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.


  1. Rini BI, et al. N Engl J Med 2019;380:1116-1127. DOI: 10.1056/NEJMoa1816714.
  2. Powles T, et al. Lancet Oncology 2020; DOI:


200O – Kondoh CN, Bae WK, Tamada S, et al. Pembrolizumab Plus Axitinib (pembro + axi) vs Sunitinib in Metastatic Renal Cell Carcinoma (mRCC) Outcomes of the KEYNOTE-426 Study in Patients From Eastern Asia. ESMO Asia Virtual Congress 2020 (20-22 November).