Brian Rini, MD, Professor of Medicine from Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center speaks about 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.
Link to Abstract
https://meetinglibrary.asco.org/record/195569/abstract
Background information:
Treatment with pembro + axi significantly improved OS, PFS, and ORR compared to sunitinib monotherapy in treatment-naive advanced ccRCC, according to the first interim analysis of the randomized, multicenter, open-label, phase 3 KEYNOTE-426 trial (NCT02853331). In this patient cohort, further follow-up (median, 30.6 mo) continued to show that pembro + axi was more effective than sunitinib monotherapy. The findings of the predetermined final analysis with a median follow-up of 42.8 months are shown below.
Methodologies:
Patients with advanced ccRCC and detectable disease (RECIST v1.1) were randomly randomized 1:1 to receive pembro 200 mg IV Q3W for up to 35 doses + axi 5 mg orally BID or sunitinib 50 mg orally QD on a 4-week on/2-week off schedule until progression, severe toxicity, or withdrawal. The IMDC risk (favorable, moderate, and poor) and geographic location were used to stratify the randomization (North America vs Western Europe vs Rest of World). OS and PFS were the two major objectives. ORR, DOR, and safety were the secondary objectives. The final analysis was based on a protocol-specified objective of 404 OS events. Because all effectiveness objectives were satisfied in the first interim analysis, no formal hypothesis testing was done; nominal P values are presented.
The following are the outcomes:
Overall, 861 points were given either pembro + axi (n=432) or sunitinib (n=429) at random. The median follow-up period, measured from randomization to the database cutoff date, was 42.8 months (range, 35.6-50.6). At the data cutoff, 418 participants had died: 193 (44.7%) of 432 participants in the pembro + axi arm and 225 (52.4%) of 429 participants in the sunitinib arm. Pembro + axi increased OS (median: 45.7 vs 40.1 mo; HR, 0.73 [95 percent CI, 0.60-0.88]; P0.001) and PFS (median: 15.7 vs 11.1 mo; HR, 0.68 [95 percent CI, 0.58-0.80]; P0.0001) when compared to sunitinib. The 42-month OS rate with pembro + axi was 57.5 percent vs 48.5 percent with sunitinib; the 42-month PFS rate with pembro + axi was 25.1 percent versus 10.6 percent with sunitinib. ORR was 60.4 percent vs 39.6 percent (P0.0001) for pembro + axi vs sunitinib; CR rate was 10.0 percent vs 3.5 percent; median DOR was 23.6 mo (range 1.4+ to 43.4+) vs 15.3 mo (range 2.3-42.8+). Anticancer treatment was given to 47.2 percent of patients in the pembro + axi arm and 65.5 percent of patients in the sunitinib arm. Despite the fact that both arms received equal amounts of VEGF/VEGFR inhibitors, only 10.2 percent of patients in the pembro + axi arm got further therapy with a PD-1/L1 inhibitor, compared to 48.7% in the sunitinib arm. There were no new safety signals found.
Final Thoughts:
This is the longest follow-up of an anti-PD–1/L1 immunotherapy coupled with a VEGF/VEGFR inhibitor for first-line RCC, with a median follow-up of 42.8 months. These findings reveal that pembro + axi is still more effective than sunitinib in terms of OS, PFS, and ORR, with no new safety signals.
NCT02853331 – http://clinicaltrials.gov/show/NCT02853331