Merck & Co.'s Keytruda in combination with Pfizer's Inlyta cuts risk of death by 47 percent in renal cancer study

Merck & Co. announced that in the Phase III KEYNOTE-426 trial, the combination of the anti-PD-1 therapy Keytruda (pembrolizumab) and Pfizer's tyrosine kinase inhibitor Inlyta (axitinib) significantly improved overall survival (OS) versus Pfizer's Sutent (sunitinib), reducing the risk of death by 47 percent, for the first-line treatment of advanced or metastatic renal cell carcinoma (RCC). Merck said in October last year that the study met both of its primary endpoints of OS and progression-free survival (PFS).

The trial randomised 861 patients with advanced or metastatic RCC to receive either Keytruda plus Inlyta, or Sutent alone as a first-line treatment. Along with the dual primary endpoints of OS and PFS, a key secondary goal was objective response rate (ORR). Further secondary endpoints include disease control rate, number of participants who experienced or discontinued the study due to an adverse event (AE), duration of response, PFS at 12, 18 and 24 months and OS at 12, 18 and 24 months.

Results from the first interim analysis, which will be presented at the Genitourinary Cancers Symposium (ASCO GU), also showed that median PFS in patients given the combination of Keytruda and Inlyta was 15.1 months, which was significantly higher than the 11.1 months seen for Sutent. Meanwhile, the ORR in the two groups was 59.3 percent and 35.7 percent, respectively. Merck noted that results across OS, PFS and ORR were consistent across all IMDC risk groups and regardless of PD-L1 expression

Roy Baynes, chief medical officer at Merck, suggested that Keytruda was the "most broad spectrum anticancer drug ever," adding that results of the KEYNOTE-426 trial showed it could be a "meaningful treatment opportunity" for patients with RCC given that its side effects were "quite manageable." In the study, 62.9 percent of patients given Keytruda plus Inlyta experienced grade 3-5 treatment-related AEs, compared to 58.1 percent for Sutent. Meanwhile, the combination regimen led to  discontinuations in 6.3 percent of patients versus 10.1 percent of thoses who received Sutent.

Commenting on the findings, Citi analyst Andrew Baum said that the combination of Keytruda and Inlyta will become the "gold standard" for treating advanced or metastatic RCC, replacing Bristol-Myers Squibb's combination of the PD-1 inhibitor Opdivo (nivolumab) and the CTLA-4 inhibitor Yervoy (ipilimumab). "We continue to believe that the market continues to under appreciate both Keytruda's potential as well as multiple other products," Baum remarked.

Last month, European regulators authorised Opdivo in combination with low-dose Yervoy for use in the first-line setting in patients with intermediate- and poor-risk advanced RCC. The approval followed clearance in the US last year, with both decisions based on findings from the CheckMate-214 trial, in which the combination of Opdivo and Yervoy reduced the risk of death by 37 percent versus Sutent.

Meanwhile, Pfizer and Merck KGaA reported results at last year's European Society for Medical Oncology (ESMO) congress from the JAVELIN Renal 101 study showing that the PD-L1 inhibitor Bavencio (avelumab) in combination with Inlyta was associated with median PFS of 13.8 months, as initial therapy for patients with advanced RCC, versus 8.4 months for Sutent. At the time, the companies noted that OS data from the trial are immature.

For related analysis, see ViewPoints: Keytruda-sized cloud threatens rare bright spot for Opdivo in RCC.

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