Pembrolizumab-axitinib combination improves outcomes in renal cell carcinoma subset
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Pembrolizumab plus axitinib continued to exhibit superior efficacy to sunitinib as first-line therapy for advanced clear cell renal cell carcinoma, according to long-term follow-up of the randomized phase 3 KEYNOTE-426 trial.
Patients who received the combination achieved longer OS and PFS. They also appeared more likely to respond to therapy.
VEGF inhibition and checkpoint inhibition are active in kidney cancer.
Many early combinations of checkpoint inhibitors and VEGF inhibitors were associated with unacceptable toxicity. However, a phase 1/phase 2 trial showed the combination of the PD-1 inhibitor pembrolizumab (Keytruda, Merck) and the VEGF-targeted tyrosine kinase inhibitor axitinib (Inlyta, Pfizer) could be an effective and safe option.
In the multicenter, open-label KEYNOTE-426 trial, Brian I. Rini, MD, professor of medicine at Vanderbilt-Ingram Cancer Center and a HemOnc Today Editorial Board member, and colleagues compared pembrolizumab-axitinib with sunitinib (Sutent, Pfizer) for treatment-naive advanced clear cell renal cell carcinoma.
The study included 861 patients (median age, 62 years; 73% men) who had Karnofsky performance scores of at least 70%.
Researchers randomly assigned 432 patients to 200 mg pembrolizumab IV every 3 weeks for a maximum 35 cycles plus 5 mg oral axitinib twice daily. The other 429 patients received 50 mg oral sunitinib daily in a 4-weeks-on, 2-weeks-off schedule. Treatment continued until disease progression, unacceptable toxicity or withdrawal.
PFS and OS served as dual primary endpoints. Secondary endpoints included objective response rate, duration of response and safety.
As Healio previously reported, results of the first interim analysis showed the pembrolizumab-axitinib combination significantly improved outcomes vs. sunitinib.
At ASCO, Rini and colleagues presented results of a prespecified final analysis. Median follow-up was 42.8 months (range, 35.6-50.6).
By data cutoff, 418 patients — 193 (44.7%) assigned pembrolizumab-axitinib and 225 (52.4%) assigned sunitinib — had died.
Patients assigned pembrolizumab-axitinib achieved significantly longer PFS (median, 15.7 months vs. 11.1 months; HR = 0.68; 95% CI, 0.58-0.8) and OS (median, 45.7 months vs. 40.1 months; HR = 0.73; 95% CI, 0.6-0.88). At 42 months, a higher percentage of patients assigned the combination remained alive (57.5% vs. 48.5%) and progression free (25.1% vs. 10.6%).
Pembrolizumab-axitinib also appeared superior with regard to ORR (60.4% vs. 39.6%; (P < .0001), complete response rate (10% vs. 3.5%) and median duration of response (23.6 months vs. 15.3 months).
A higher percentage of patients assigned sunitinib received subsequent anticancer therapy (65.5% vs. 47.2%). A similar percentage of patients in each treatment group received subsequent therapy with VEGF/VEGFR inhibitors; however, a considerably higher percentage of patients assigned sunitinib than pembrolizumab-axitinib received subsequent PD-1/PD-L1 inhibitor treatment (48.7% vs. 10.2%).
Researchers observed no new safety signals with the pembrolizumab-axitinib combination.
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Rini BI, et al. Abstract 4500. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
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