Rarely do two similar and hugely important trials yield results so close together, but this is exactly what happened at Asco this year. Pivotal tests of Roche and Merck & Co’s competing checkpoint inhibitors in front-line squamous lung cancer were presented and, statistically speaking, it is hard not to chalk this one up to Merck.
Still, closer examination of the data reveals numbers that look remarkably similar and physicians were broadly positive about both studies. If Roche manages eventually to tease an overall survival benefit from its trial, it will be much tougher to call a winner.
Based on data presented by Roche so far, from the Impower131 study, it is far from certain that an overall survival benefit will be seen with the company's contender, Tecentriq. Too few deaths had occurred to trigger the final analyses, which Roche hopes to have later this year (Asco 2018 – Roche sets a low bar for Merck to beat, June 2, 2018).
Given that patients only survive a matter of a couple of months, this remains a very important measure to hit. Merck managed to show a pretty unequivocal benefit with Keytruda in Keynote-407, however, and for now this will stand that drug in very good stead in this tough-to-treat cancer subset.
|Squamous lung cancer - the results so far|
|Arm B (Tecentriq + carbo + Abraxane; n = 343)||Arm C (carbo + Abraxane; n = 340)||Keytruda + chemo (n=101)||Chemo (n=103)|
|Median PFS (months)||6.3||5.6||6.4||4.8|
|HR and p value for PFS||0.715; 0.0001||0.56; 0.0001|
|Median OS (months)||14||13.9||15.9||11.3|
|HR and p value for OS||Not significant||0.64; 0.0008|
|Source: Asco presentations|
“They are both very promising outcomes,” Dr David Graham, of the Levine Cancer Institute, told EP Vantage. “[On Impower131] we need to see overall survival ... so we have something that gives us stronger evidence [in Keynote-407].”
“But what's really impressive is that both of these studies fly in the face of what we believe our common knowledge to be – that you had to have higher PD-L1 expression to get a benefit from immunotherapy [in squamous] – and that seems to be wrong.”
In a pre-specified but exploratory endpoint, Merck reported impressive hazard ratios across PD-L1 subsets. Roche included PD-L1 as a stratified factor and found the same result – top-line data were released on Saturday, and full results from Impower131 will be reported on Monday.
Merck also said it observed a survival benefit across all patient subgroups it measured, including age, sex and type of chemotherapy backbone.
|Keynote-407 results by PD-L1 status|
Dr Graham said it was not immediately clear why PD-L1 expression seems not to be important in squamous lung cancer. And even though the benefit of these therapies looks modest in terms of months, he pointed to the very minimal additional toxicities that they add.
“The medians may seem like a relatively short time, but the chance that a patient does not progress after a year doubles when you add immunotherapy. So for person to achieve a life mark, whether that be a holiday or a birthday, without having to undergo a great amount more toxicity, to achieve that life mark can be extremely important,” he said.
Merck has already filed for FDA approval in squamous disease and looks pretty certain to get a green light. Roche told EP Vantage that it is discussing the results with regulators, but acknowledged that an overall survival finding would be needed to support the filing, and compete with Keytruda.
Merck can claim victory in another lung cancer niche for now. By the end of the year it will know whether it has the space to itself.