Pembrolizumab Gets Breakthrough Designation for NSCLC Indication

The FDA granted breakthrough therapy designation to pembrolizumab (Keytruda), an anti-PD-1 agent for the treatment of patients with non-small-cell lung cancer who do not have EGFR mutations or ALK rearrangements.

The US Food and Drug Administration (FDA) granted breakthrough therapy designation to pembrolizumab (Keytruda), an anti–PD-1 agent for the treatment of patients with non–small-cell lung cancer (NSCLC) who do not have EGFR mutations or ALK rearrangements. It is also only intended for those whose disease has progressed during or after treatment with platinum-based chemotherapy.

“The FDA’s breakthrough therapy designation of Keytruda underscores that new treatment approaches for advanced NSCLC continue to be needed,” said Merck’s president Roger Perlmutter, MD, PhD, in a press release. “Our data investigating the use of Keytruda in this difficult-to-treat malignancy are very encouraging, and we look forward to working closely with the FDA to expedite our clinical program.”

Pembrolizumab is already approved in the United States for treatment of unresectable or metastatic melanoma. Breakthrough designation for the new indication in NSCLC would allow for more rapid evaluation and approval; the melanoma indication also came out of a breakthrough designation.

The drug blocks both PD-L1 and PD-L2, which are expressed mostly on activated T cells. Expression of PD-L1 on tumor cells and macrophages suppresses immune activity and permits malignant growth. Results from the KEYNOTE-001 study were presented recently at the European Society of Medical Oncology meeting; it included 282 patients with NSCLC.

Among 262 patients with available data over a median of 5.4 months of follow-up, the progression-free survival (PFS) among treatment-naive patients was 27 weeks. In previously treated patients, however, the PFS was 10 weeks. The median overall survival (OS) was not yet reached in the treatment-naive patients and was 8.2 months in the previously treated patients. In the overall pooled population, PFS was 13 weeks with a 24-week PFS rate of 30%, and the median OS was 8.2 months with a 6-month OS rate of 64%.

Response rates were higher in patients with strong PD-L1 expression based on staining assays than in those with weaker expression. PFS and OS were also both longer in those with stronger PD-L1 expression. The drug was well tolerated, with grade 3-5 drug-related adverse events occurring in 9% of patients; the most common such event was pneumonitis.

Pembrolizumab is currently being studied across a wide array of malignancies. These include active or soon-to-be-active trials in renal cell cancer, urothelial cancer, head and neck squamous cell carcinoma, multiple myeloma, and others. Merck reports that they are examining the drug’s effects across as many as 30 types of cancer.