medwireNews: For patients with treatment-naïve advanced renal cell carcinoma, pembrolizumab plus axitinib offers superior overall survival (OS) to sunitinib, confirms an updated analysis from the KEYNOTE-426 trial.
The efficacy and safety results were presented at the virtual 2020 ASCO Annual Meeting by Elizabeth Plimack, from Fox Chase Cancer Center in Philadelphia, Pennsylvania, USA, and follow on from the interim analysis findings after a minimum of 7 months of follow-up that were presented at ASCO GU 2019.
After a minimum of 23 months, median OS in the intention-to-treat population was unreached for the 432 patients randomly assigned to receive 35 cycles of pembrolizumab 200 mg every 3 weeks plus axitinib 5 mg twice daily versus 35.7 months for the 429 patients instead given sunitinib 50 mg for the first 4 weeks of each 6-week cycle.
This gave a significant hazard ratio (HR) for death of 0.68 in favor of pembrolizumab plus axitinib, Plimack told delegates, with 24-month rates of OS of 74% and 66% in the combination and monotherapy arms, respectively.
Progression-free survival (PFS) also significantly favored pembrolizumab plus axitinib versus sunitinib, with median durations of 15.4 versus 11.1 months and a HR for death or progression of 0.71. The 24-month rates were a corresponding 38% and 27%.
In addition, patients given the combination had a higher confirmed objective response rate (ORR) than those given monotherapy (60.2 vs 39.9%) and had a longer median duration of response (23.5 vs 15.9 months).
When patients were grouped by IMDC risk, a significant OS benefit with pembrolizumab plus axitinib was found for those with intermediate/poor risk (HR=0.63) but not those with a favorable status. Plimack remarked that it will be “important” to watch the favorable risk survival curve over the next 3 years to see if the treatment arm curves separate for this subgroup.
PFS was also significantly better with the combination arm, only in the intermediate/poor risk group (HR=0.69), but the favorable group had a better ORR with pembrolizumab plus axitinib versus sunitinib than did the intermediate/poor group (69.6 vs 50.4% and 55.8 vs 35.2%, respectively).
Discussing the safety data, Plimack said there were “slightly more” grade 3–5 treatment-related adverse events among patients given pembrolizumab plus axitinib versus sunitinib (66.9 vs 62.4%), and “few” treatment-related deaths in either arm (4 vs 6).
Discussing the adverse events of special interest, the presenter said the overall rate of grade 3–5 events in the combination arm was “around 15%”, most commonly hepatitis, colitis, and severe skin reactions.
“Each individual incidence is low but taken together, the incidence remains significant and we need to counsel patients on immunotherapy to watch for these”, she emphasized.
Finally, Plimack reported the findings of the 6-month landmark analysis of the relationship between depth of response and survival, showing survival curves to demonstrate that patients who achieved a complete response (CR) with either treatment regimen “do very well.”
And among patients with a near CR, defined as 80% or higher, those given pembrolizumab plus axitinib “do almost as well as those with CR,” she said, but this pattern was not found in the sunitinib arm.
“These results continue to support pembrolizumab plus axitinib as a standard of care for patients with previously untreated advanced renal cell carcinoma,” the presenter concluded.
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This independent news story was supported by an educational grant from Pfizer and Merck KGaA