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First-line pembrolizumab/axitinib sustains survival benefit in kidney cancer


At a median follow-up of over 2.5 years, the combination continued to show a significant benefit in overall and progression-free survival versus single-agent sunitinib.

The frontline combination of pembrolizumab (Keytruda) plus axitinib (Inlyta) continued to show a survival benefit over single-agent sunitinib (Sutent), according to long-term follow-up data from the phase 3 KEYNOTE-426 trial published in the Lancet Oncology.1

At a median follow-up of 30.6 months, the median overall survival (OS) had not yet been reached with pembrolizumab/axitinib compared with 35.7 months with sunitinib monotherapy (HR, 0.68; P = .0003). The combination also significantly improved progression-free survival (PFS) with a median PFS of 15.4 months compared with 11.1 months with sunitinib (HR, 0.71; P <.0001).

“These results continue to support the first-line treatment with pembrolizumab plus axitinib as the standard of care of advanced renal cell carcinoma,” study author Thomas Powles, MD, MBBS, MRCP, director, Barts Cancer Institute, and coauthors wrote.

Based on prior data from the KEYNOTE-426 trial, the FDA approved the immunotherapy pembrolizumab plus the multikinase inhibitor axitinib in April 2019 for use in the frontline setting for patients with advanced RCC.

The international, open-label, phase 3 KEYNOTE-426 study (NCT02853331) included 861 patients aged ≥18 years with treatment-naive, advanced RCC. All patients had clear cell histology. Patients were randomized between October 24, 2016, and January 24, 2018, to either pembrolizumab plus axitinib (n = 432) or single-agent sunitinib (n = 429). OS and PFS were the primary study end points.

The most common grade ≥3 treatment-related adverse events were hypertension (22% in the combination arm vs 20% in the sunitinib arm), alanine aminotransferase increase (13% vs 3%, respectively), and diarrhea (11% vs 5%, respectively).

In an accompanying commentary in the Lancet Oncology,2 Giuseppe Procopio, MD, Federico Nichetti, MD, and Elena Verzoni, MD, department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, noted that the pembrolizumab/axitinib results must be assessed in the context of other key studies of immunotherapy plus VEGF inhibitors in advanced RCC.

“Data from the KEYNOTE-426 study must be read and interpreted together with the existing published literature, and in particular with the CheckMate 214 trial (nivolumab [Opdivo] plus ipilimumab [Yervoy] vs sunitinib), the JAVELIN Renal 101 trial (avelumab [Bavencio] plus axitinib vs sunitinib), and the IMmotion151 trial (atezolizumab [Tecentriq] plus bevacizumab [Avastin] vs sunitinib),” the authors wrote.

“Given the impossibility of making direct comparisons between the different combinations, clinical experience and confidence with one combination over another is the best way…to choose between these therapeutic options according to evidence-based recommendations,” they added.

Additional trials that will further cloud this treatment landscape include the CheckMate-9ER study of nivolumab plus cabozantinib versus sunitinib, as well as the CLEAR study examining lenvatinib (Lenvima) plus either pembrolizumab or everolimus (Afinitor) against a control arm of single-agent sunitinib.


1. 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 [published online October 23, 2020]. Lancet Oncol. doi.org/10.1016/S1470-2045(20)30436-8

2. Procopio G, Nichetti F, Verzoni E, et al. Pembrolizumab plus axitinib: another step ahead in advanced renal cell carcinoma [published online October 23, 2020]. Lancet Oncol. doi: 10.1016/S1470-2045(20)30482-4

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