Merck’s immune-boosting cancer drug, Keytruda, bested the standard of care in advanced melanoma, the deadly skin cancer, and showed promising results in non-small cell lung cancer.
Based on these data, Merck says it has filed an application with the Food and Drug Administration for Keytruda to be used in non-small cell lung cancer, and will soon file for it to be used as a first option in melanoma. The company had earlier issued a press release on the skin cancer result.
The full data, published in the New England Journal of Medicine and presented here in Philadelphia at the annual meeting of the American Association for Cancer Research, further bolster the prospects of a drug that last year came from behind in a heated race with Bristol-Myers Squibb to become the first medicine of its kind to reach the market. That follows another Bristol immune therapy, Yervoy, that was approved in 2011, and comes as swath of immune-boosting therapies are changing the way scientists are thinking about treating cancer.
“I think we are watching a revolutionary change in cancer therapy,” says Roger Perlmutter, Merck’s head of research and development. “Certainly the most important advance in my lifetime and maybe the most important advance since the introduction of radiotherapy.”
In melanoma, 834 patients were assigned to receive Keytruda every two weeks, Keytruda every three weeks, or to receive Yervoy. Forty-seven-point-three percent of the patients on Keytruda every two weeks had not seen their cancer advance; the same for 46.4% of those who received every three weeks. For those on Yervoy, that rate was just 26.5%. That equates to about a 42% reduction in the risk of disease progression.
“This is now expected to change the treatment landscape for melanoma,” said Suzanne L. Topalian of Johns Hopkins University at an AACR press conference.
“Again and again, new immune therapies are producing meaningful outcomes for our patients, and doing so in an altogether different and more durable way than conventional treatments,” writes Robert Vonderheide, the associate director of the Abramson Cancer Center at the University of Pennsylvania, via email. “The breakthrough drug approved 4 years ago is now seemingly surpassed, with less toxicity.”
But Perlmutter readily concedes that so far Merck’s medicine has “more in common than in conflict” with Bristol’s rival Opdivo. It’s estimated that at 12 months 74% of patients on Keytruda will still be alive; in a study testing Opdivo against a chemotherapy treatment, that rate was 73%.
The race is on in lung cancer, too, where on Friday Bristol-Myers Squibb announced, without releasing details, that a study had shown Opdivo reduces the death rate in the non-squamous form of non-small cell lung cancer. An earlier study had shown a positive result in the squamous form, and the FDA approved the drug for that use in March.
Merck is betting that it can get approved in lung cancer without comparing to a control group by proving that it can select for patients who are most likely to benefit from Keytruda. Both Opdivo and Keytruda work by blocking a protein called the programed cell death receptor (PD-1), which prevents the immune system from destroying cells, including cancer cells. PD-1 drugs seem to work better in patients whose cancer cells are covered with the receptor PDL1, which is what PD-1 binds to.
Merck has received a “breakthrough” designation, designed to speed approval for using Keytruda with a PDL1 diagnostic made by Agilent – and Perlmutter says he does not think it could be revoked because of the Bristol results.
“Our breakthrough designation is based on our ability to define a population that is especially responsive using the PDL1 biomarker and being careful about having a test set and a balance set,” Perlmutter says. “That’s quite a different thing from looking at an all-comers overall survival study.”
The lung cancer study enrolled 495 patients who all got one of three different doses of Keytruda. Tumors dyed with a stain that turns brown with PDL1. For patients who had more than 50% PDL1, tumors shrank or remained stable 45% of the time. That compares to 16.5% for those who had PDL1 on less than 50% of their cells and 10.7% for those who had little detectable PDL1.
Patients with high PDL1 expression were able to live longer four months longer without their cancer worsening than those with little PDL1. The median patient on the other treatments lived 8.8 months. That number has not been reached for those with lots of PDL1 expression, although the number will be at least five months longer.
Antoni Ribas, the UCLA doctor who led Merck’s melanoma study, said that the next big question is how to get the PD-1 blockers approved in the rest of the world, where regulatory agencies have not moved as quickly as the FDA.
Source: Forbes Health