The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Pembrolizumab plus axitinib (pembro-axi) continued to demonstrate superior efficacy compared with sunitinib as first-line therapy in advanced clear cell renal cell carcinoma (ccRCC), according to updated results from the KEYNOTE-426 trial presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.1

The trial ( Identifier: NCT02853331) included 861 patients with advanced ccRCC who were randomly assigned to receive pembro-axi (n = 432) or sunitinib (n = 429).

Investigators defined median duration of follow-up as the time from randomization to the database cutoff date. At the data cutoff, 418 patients had died — 193 (44.7%) in the pembro- axi arm and 225 (52.4%) in the sunitinib arm. No new safety signals were identified.

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In the first interim analysis of the trial, pembro-axi significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared with sunitinib.2 Extended follow-up at a median of 30.6 months again showed superior efficacy of the combination treatment.3

Findings from the new analysis, done at a median follow-up of 42.8 months, reinforced that the combination therapy “is an acceptable front-line standard,” investigator Brian I. Rini, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, stated in an interview.

The 42-month OS rate was 57.5% in the pembro-axi arm compared with 48.5% in the sunitinib arm, Dr Rini reported. The 42-month PFS rates were 25.1% and 10.6%, respectively.

Compared with sunitinib, pembro-axi was associated with a 27% decreased risk of death (95% CI, 0.60-0.88; P <.001) and a 32% decreased risk of progression or death (95% CI, 0.58-0.80; P <.0001).

Patients in the pembro-axi arm had a significantly higher ORR compared with patients in the sunitinib arm (60.4% vs 39.6%). Patients in the pembro-axi arm also had a higher complete response rate (10.0% vs 3.5%) and a longer median duration of response (23.6 months vs 15.3 months).

The rate of treatment discontinuation was higher in the sunitinib arm than in the pembro-axi arm (90.6% vs 81.4%), as was the proportion of patients who received subsequent therapy (73.0% vs 58.4%).

Asked if he had any advice for clinicians prescribing pembro-axi, Dr Rini emphasized that axitinib is an important part of the treatment, and clinicians should resist a temptation to discontinue it early.

As with other tyrosine kinase inhibitors, axitinib can be titrated up and down easily to arrive at what is tolerable for patients in the short and long term, he explained. Studies have established that dual therapy is better than single therapy, so “it is worth putting in the effort to keep patients on both drugs,” Dr Rini said.

Disclosures: This research was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


  1. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): results from 42-month follow-up of KEYNOTE-426. J Clin Oncol. 2021;39:(suppl 15; abstr 4500). doi:10.1200/JCO.2021.39.15_suppl.4500 
  2. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380:1116-1127. doi:10.1056/NEJMoa1816714
  3. Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1563-1573. doi: 10.1016/S1470-2045(20)30436-8.