Updated data from the KEYNOTE-426 trial was presented at the ASCO 2020 Virtual Annual Meeting
Previous results from KEYNOTE-426, a phase III randomized, open-label trial (NCT02853331), had demonstrated – in the minimum follow-up of 7 months – overall survival gain (OS), progression-free survival (PFS) and response rate in comparison of pembrolizamb plus axitinib versus sunitinib in the first line of treatment for patients with clear cell renal cell carcinoma (cRCC). The 27-month mean follow-up analyzes were presented at the ASCO 2020 Virtual Annual Meeting.
Patients with untreated RCC, with Karnofsky performance status (KPS) ≥70% and measurable disease (RECIST v1.1) were randomly allocated 1: 1 to receive pembrolizumab 200 mg EV every 3 weeks for up to 35 doses + axitinib 5 mg by VO 2x / day (arm P + A) or sunitinib 50 mg VO daily in a regimen of 4 weeks yes and 2 weeks no (arm S) until progression, toxicity or study exit.
Randomization was stratified by IMDC risk (favorable versus intermediate versus unfavorable) and geographic region (North America versus Western Europe versus the rest of the world). The primary endpoints were OS and PFS. The secondary endpoints were response rate, duration of response (DDR) and safety.
A total of 861 patients were randomly assigned to the P + A arm (n = 432) and to the S arm (n = 429). The median follow-up time for all patients was 27.0 months (0.1-38.4).
The association of P + A demonstrated gain in OS compared to S (HR, 0.68 [95% CI, 0.55-0.85]; p <0.001; OS in 24 months, 74% versus 66%). The median OS (95% CI) was not achieved with P + A and was 35.7 months (33.3-NR) with S. The P + A association improved the PFS versus S (HR, 0.71 [CI 95%, 0.60-0.84]; p <0.001; PFS at 24 months, 38% versus 27%). For P + A versus S, respectively, the median PFS (95% CI) was 15.4 (12.7-18.9) versus 11.1 months (9.1-12.5); the RR was 60% versus 40% (p <0.0001); the complete response rate was 9% versus 3%; and the median DDR was 23.5 months (range 1.4+ to 34.5+) versus 15.9 months (range 2.3-31.8 +).
In general, the P + A benefit was observed in all evaluated subgroups, including subgroups stratified according to IMDC risk and subgroups by expression of PD-L1. The 6-month post-hoc analysis showed that patients with a ≥80% reduction in the target lesion in the P + A arm had an OS similar to that of patients with complete response by RECIST v1.1, according to the Kaplan- Meier and Hazard Ratio [95% CI] estimated (0.20 [0.05-0.84] vs. 0.10 [0.01-0.76], respectively), compared to patients aged 0-30 % reduction in target injury. No new adverse effects were detected.
P + A continue to demonstrate superior and durable antitumor activity versus S monotherapy in patients with RCC as first-line treatment, according to the mean follow-up data of 27 months.
J Clin Oncol 38: 2020 (suppl; abstr 5001). DOI:10.1200/JCO.2020.38.15_suppl.5001
Clinical trial information: NCT02853331.