KEYNOTE-426 subgroup analyses confirm pembrolizumab–axitinib efficacy
medwireNews: Research presented at the 2019 ASCO Annual Meeting in Chicago, Illinois, USA, adds support for use of pembrolizumab plus axitinib as a first-line treatment for patients with metastatic renal cell carcinoma (RCC).
Favorable overall survival (OS) results for the KEYNOTE-426 trial were previously reported 16487976for the combination compared with sunitinib monotherapy in patients with treatment-naïve, newly diagnosed or recurrent stage IV clear cell disease, leading to US FDA approval 16679254 of pembrolizumab plus axitinib in the first-line setting.
For this update, Brian Rini (Cleveland Clinic, Ohio, USA) gave findings for the depth-of-response analysis in patients with at least one RECIST imaging assessment after treatment showing that 94% of 396 patients receiving pembrolizumab plus axitinib experienced a reduction in their target lesion from baseline compared with 85% of the 388 sunitinib-treated counterparts.
The corresponding rates for a 30% or greater reduction, and a 60% or greater reduction in target lesion size were 77% versus 50% and 42% versus 16%, with 17% and 6% experiencing at least an 80% reduction, respectively. A complete response was achieved by 9% and 3%.
For the subgroup of patients with IMDC favorable risk, 95% of the pembrolizumab plus axitinib and 94% of the sunitinib arms were alive at 12 months and the hazard ratio (HR) for death of 0.64 was not significant.
There was a 5-month difference in median progression-free survival (PFS) between the treatment arms after around a third of patients in both the combination and sunitinib arms had experienced events (17.7 vs 12.7 months, nonsignificant HR=0.81) and the objective response rate (ORR) was 66.7% versus 49.6%.
Among patients with IMDC intermediate/poor risk, OS significantly favored pembrolizumab plus axitinib with a HR of 0.52 and a 16 percentage point difference in 12-month survival (87 vs 71%). A significant benefit was also found for PFS (median 12.6 vs 8.2 months, HR=0.67) and the ORR was almost doubled with the combination strategy (55.8 vs 29.5%).
Sarcomatoid features occurred in 51 patients given pembrolizumab plus axitinib and 54 given sunitinib, with these patients more commonly classified as IMDC intermediate or poor risk, and positive for PD-L1 expression than the full study population.
The ORR in the sarcomatoid subgroup with the combination and sunitinib was 58.8% versus 31.5% including a compete response in 13.0% versus 2.0%.
And Rini commented that the depth of response results were “remarkable” with just one patient with measurable disease given pembrolizumab plus axitinib not achieving a decrease in target lesion size, giving a rate of 98% compared with 80% of sunitinib-treated patients. The corresponding rates of 30%, 60%, and 80% or greater reductions of target lesions were 80% versus 50%, 54% versus 16%, and 33% versus 8%.
The HR for OS was 0.58 in favor of the combination treatment in patients with sarcomatoid features but had wide confidence intervals, although Rini noted that “a relatively small number” of patients have died, and the median OS is yet to be reached in either arm.Analysis of PFS gave a 12-month rate of 57% with pembrolizumab plus axitinib versus 26% with sunitinib, with the median duration unreached versus 8.4 months, giving a HR of 0.54 albeit that the upper bound of the confidence interval was 1.0.
“We start to see a late separation of the curves as is typical of immunotherapy with about a doubling of the [PFS) rate”, the presenter continued.
Rini concluded: “Pembrolizumab plus axitinib is a new standard of care for first-line treatment of advanced clear-cell RCC, with OS, PFS and ORR benefit in all IMDC risk categories and substantial activity in participants with sarcomatoid RCC.”
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