Merck & Co has unveiled a new trial supporting the benefits of its lung cancer drug Keytruda, but is still lagging behind rival Bristol-Myers Squibb in the data stakes.
The KEYNOTE-010 study showed that PD-1 inhibitor Keytruda (pembrolizumab) was able to extend overall survival compared to chemotherapy drug docetaxel in advanced non-small-cell lung cancer (NSCLC), both at the approved 2mg/kg dose and an investigational 10mg/kg dose.
The higher dose of Keytruda did not appear to provide any additional benefit over the approved regimen, according to Merck.
However, the phase II/III study misfired on its secondary endpoint, as it was unable to show a significant improvement over docetaxel on progression-free survival in a subgroup of patients whose tumours were PD-L1 positive.
While the overall survival data is more important, the hiccup in the data does not help Keytruda compete with BMS’ Opdivo (nivolumab), which recently scored another approval in second-line NSCLC therapy that gives it a broader label claim than Merck’s drug.
Keytruda is only cleared for use in patients whose tumours test positive for PD-L1, while Opdivo can be prescribed regardless of PD-L1 status.
The FDA has however indicated that there are still a lot of unknowns when it comes to the clinical relevance of the biomarker, and it is notable that KEYNOTE-010 did show that the drug was effective in patients with lower levels of PD-L1 expression. That raises the possibility that its label could be extended, and Merck said it intends to seek FDA approval for that later this year.
Moreover, both Merck and BMS are testing their drugs as first-line therapies for NSCLC based on PD-L1 status, and drugs could compete on a level playing field in this much larger patient population.
Meanwhile, the label issue may not be as significant as some think, because oncologists tend to exercise a good deal more autonomy in prescribing decisions than other medical disciplines. For example, if the National Cancer Care Network (NCCN) includes Keytruda in its recommendations, then it will be used and – importantly – Medicare is beholden to cover all NCCN-backed medicines.
Nevertheless, for now analysts are putting BMS out in front, with 2020 sales of more than $8bn for Opdivo, ahead of a $5bn expectation for Keytruda. With dozens of studies still to generate results in the intervening years however predicting the eventual winner in the checkpoint inhibitor is a tough call.