By Anette Breindl, Senior Science Editor .
PHILADELPHIA – Patients treated with Merck & Co Inc.’s Keytruda (pembrolizumab) had better outcomes than could be achieved with their respective standards of care in melanoma and lung cancer trials. Results were presented today at the annual meeting of the American Association for Cancer Research (AACR).
Full data from the Keynote-006 study, a head-to-head comparison of Keytruda (Pembrolizumab, Merck & Co Inc.) and Yervoy (ipilimumab, Bristol-Myers Squibb Co.) for the treatment of metastatic melanoma, showed that Keytruda was “superior on all counts” to Yervoy, Keynote-006 study lead Antoni Ribas said.
Patients receiving Keytruda had better overall survival, better progression-free survival, a higher overall response rate and lower rates of adverse reactions.
The findings “should change the paradigm of treatment … the standard of care should quickly shift to giving a PD-1 antibody,” Ribas said. He noted that although the Keynote-006 trial tested Keytruda, he believes similar effects would be achieved with Opdivo (nivolumab, Bristol-Myers Squibb Co.), which also targets PD-1.
This should also lead to label changes for the drug, which is so far approved for use only after both Yervoy and Zelboraf have failed.
“I assume with this data the FDA will soon change the label,” Ribas said, although he added that Medicare already allows up-front use of Keytruda, and so “the field is going a little bit faster than the FDA.”
The somewhat surprising label reflects partly how young the immunotherapy space still is in terms of its regulatory history. (See BioWorld Today, Sept. 7, 2014.)
When Keytruda was approved, Merck’s senior vice president of global clinical development Roy Baynes told BioWorld Today, “the unmet need was in patients who had failed Yervoy.”
But the new data show, Baynes said, that Keytruda is “superior” to Yervoy, and the company is seeking its approval for metastatic melanoma patients who have not previously been treated with Yervoy.
In the Keynote-006 trial, 834 patients with metastatic melanoma were randomly assigned to one of the treatment arms. They either received Yervoy, or Keytruda dosed every two or three weeks. The Keynote-006 trial was halted early in March after an interim analysis indication that the trial had met its primary and secondary endpoints of overall and progression-free survival, respectively.
At AACR, Ribas, presented the details of the trial, which were concurrently published in the April 19, 2015, online issue of The New England Journal of Medicine.
Overall survival at one year for patients who received pembrolizumab was 74 percent and 68 percent in the two Keytruda groups, significantly higher than the 58 percent for patients treated with Yervoy. After six months, the response rate was 45 percent for patients taking Keytruda compared to 26 percent for those who received Yervoy. Overall response rates were at about 33 percent for both Keytruda groups, as opposed to 12 percent for Yervoy.
Keytruda also improved overall survival in lung cancer patients treated with the drug. Edward Garon showed data from the Keynote-001 non-small cell lung cancer expansion cohort, nearly 500 patients were treated with Keytruda.
Not surprisingly, the patients with the highest levels of PD-L1 staining benefited most from the treatment.
Compared to chemotherapy, such patients had a higher response rate, and the median overall survival ‑ which was less than nine months for patients with intermediate or low levels of PD-L1 ‑ has not yet been reached for patients with high levels of PD-L1 expression on their tumors.
In patients with high levels of PD-L1, 45 percent responded to the drug. Merck announced on Sunday that it has filed a supplementary biologics license application for Keytruda in advanced non-small cell lung cancer based on the trial results.
Garon said that benefit “substantially exceeds that expected from chemo” in patients with high staining tumors, but is still “compelling” for patients with intermediate levels of staining.
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