Keytruda (pembrolizumab) can now be used in combination with chemotherapy — Paraplatin (carboplatin) plus Taxol (paclitaxel) or Abraxane (nab-paclitaxel) — as first-line therapy for patients with metastatic squamous non-small cell lung cancer (NSCLC) in the United States.
This expanded use, granted by the U.S. Food and Drug Administration (FDA), comes after promising data in the KEYNOTE-407 Phase 3 trial (NCT02775435), where the combination significantly extended the lives of patients compared to chemotherapy alone.
“Today’s approval expands our current lung cancer indications to include combination treatment in patients with squamous cell carcinoma, a type of lung cancer that is particularly difficult to treat,” Roger Perlmutter, MD, PhD, president of Merck Research Laboratories, said in a press release.
Keytruda, developed by Merck (known as MSD outside the U.S. and Canada), is an approved immunotherapy for the first-line treatment of metastatic non-squamous NSCLC patients, in combination with Alimta (pemetrexed) and platinum-based chemotherapy.
It works by counteracting a mechanism used by cancer cells to evade anti-cancer immune responses. This mechanism involves the production of PD-L1 by tumor cells to interact with the PD-1 receptor on the surface of specific immune cells, which “shuts down” the immune response against them.
By suppressing PD-1/PD-L1 interaction, Keytruda restores the body’s capacity to activate an anti-tumor response and fight cancer cells.
KEYNOTE-407 was designed to determine if Keytruda could also improve outcomes in untreated squamous lung cancer patients when given in combination with chemotherapy.
To date, 559 patients have been enrolled in the trial, and received either standard chemotherapy — Paraplatin plus Taxol or Paraplatin plus Abraxane — or chemotherapy in combination with Keytruda.
As primary goals, researchers aimed to determine if Keytruda improved the time patients lived without signs of disease worsening and extended their survival. A key secondary measure was the proportion of patients achieving a partial or complete response.
An analysis of the first 204 patients had shown that more people responded to Keytruda (58%) than to chemotherapy alone (35%).
Now, researchers report that Keytruda extended the time patients lived without disease progression from 4.8 to 6.4 months, representing a 44% reduction in the risk of disease worsening or death. Patients on Keytruda also lived longer (15.9 months) than those receiving chemotherapy alone (11.3 months) — suggesting a 36% reduction in the risk of death.
Importantly, the improvements were independent of patients’ PD-L1 status — a biomarker often used as a predictor of responses to PD-1/PD-L1 inhibitors.
“With this important approval, more patients will have the opportunity to benefit from immunotherapy,” said Balazs Halmos, MD, director of the multidisciplinary thoracic oncology program at the Montefiore Einstein Center for Cancer Care.
The FDA is also reviewing Keytruda as a stand-alone treatment for metastatic, squamous or non-squamous NSCLC patients without EGFR or ALK mutations, and whose tumors produce the PD-L1 factor.