The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency (EMA), has recommended the approval of Keytruda (pembrolizumab) in combination with chemotherapy for the initial treatment of metastatic squamous non-small cell lung cancer (NSCLC) patients.
The CHMP’s opinion was based on clinical evidence from the KEYNOTE-407 Phase 3 trial (NCT02775435), in which the combination significantly extended patients’ lives compared to chemotherapy alone. It now will be reviewed by the European Commission for a final decision regarding approval, which is expected by April.
“We are pleased by today’s positive opinion from the CHMP, which brings us one step closer to potentially expanding our lung cancer indications in Europe to include first-line combination therapy for patients with metastatic squamous non-small cell lung cancer, regardless of PD-L1 expression,” Roy Baynes said in a press release. Baynes is senior vice president and head of global clinical development, and chief medical officer, Merck Research Laboratories.
“This is important as squamous cell carcinoma continues to be an area of unmet need, and there was a significant overall survival benefit observed in the Phase 3 KEYNOTE-407 trial,” Baynes said.
Keytruda, developed by Merck (the company is known as MSD outside the U.S. and Canada), is an immunotherapy that works by counteracting a mechanism hijacked 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 interactions, Keytruda restores the body’s capacity to activate an anti-tumor response and fight cancer cells.
Keytruda is already approved for the first-line treatment of metastatic non-squamous NSCLC patients, in combination with Alimta (pemetrexed) and platinum-based chemotherapy.
KEYNOTE-407 was designed to determine if Keytruda also could improve the outcomes of squamous NSCLC patients when added to standard first-line chemotherapy.
The trial recruited 559 patients who were assigned randomly Keytruda plus chemotherapy — Paraplatin (carboplatin) and Taxol (paclitaxel) every three weeks, or weekly Abraxane (nab-paclitaxel) — or a placebo plus chemotherapy. Chemotherapy was given for four, three-week cycles, while Keytruda treatment lasted up to 35 cycles.
Researchers aimed to determine if Keytruda improved the time patients lived without signs of disease worsening and extended their survival. Additional, secondary goals included the proportion of patients achieving a partial or complete response and safety.
After a median follow-up of 7.8 months, more people had responded to Keytruda (57.9%) than to chemotherapy alone (38.4%). Responses also were longer for Keytruda — 6.3 months versus 4.7 months.
Patients receiving Keytruda lived a median of 6.4 months without signs of disease progression, compared to 4.8 months for chemotherapy alone. Overall survival also was longer for Keytruda (15.9 months versus 11.3 months). This represented a 44% reduction in the risk of death or disease worsening and a 36% lower risk of death.
This benefit was seen across multiple patient subgroups, and regardless of PD-L1 status (a biomarker that often predicts responses to Keytruda), site of recruitment, and type of chemotherapy.
In the trial, most patients in both groups experienced an adverse side effect. Serious side effects were similar in both groups — 69.8% versus 68.2%. However, more patients on Keytruda discontinued treatment due to adverse side effects – 13.3% versus 6.4%.
In November 2018, a combination of Keytruda and chemotherapy was approved by the U.S. Food and Drug Administration (FDA) for the first-line treatment of metastatic squamous NSCLC patients. The approval also was supported by KEYNOTE-407 data.
