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FDA Expands Indication for Pembrolizumab to Metastatic Small Cell Lung Cancer


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ON JUNE 17, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the anti– programmed cell death protein 1 (PD-1) therapy pembrolizumab (Keytruda) as monotherapy for patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. This approval marks the first indication for pembrolizumab in SCLC; the drug was granted Orphan Drug designation for SCLC in October 2017.

This Priority Review and approval were based on tumor response rate and durability of response data from the KEYNOTE-158 and KEYNOTE-028 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Two KEYNOTE Trials

THE APPROVAL was based on pooled data from KEYNOTE-158 (cohort G) and KEYNOTE-028 (cohort C1), two multicenter, multicohort, nonrandomized, open-label trials evaluating pembrolizumab in patients with SCLC who had disease progression during or after platinum-based chemotherapy and at least one other prior line of therapy. Patients evaluated for efficacy received either pembrolizumab at 200 mg intravenously every 3 weeks (n = 64) or at 10 mg/kg intravenously every 2 weeks (n = 19). Treatment continued until documented disease progression, unacceptable toxicity, or a maximum of 24 months.

The major efficacy outcome measures were objective response rate and duration of response, as assessed by blinded independent central review according to modified Response Evaluation Criteria in Solid Tumors, version 1.1. Pembrolizumab demonstrated an objective response rate of 19% (95% confidence interval = 11%–29%), with a complete response rate of 2% and a partial response rate of 17%. Among the 16 responding patients, 94% had a response of 6 months or longer, 63% had a response of 12 months or longer, and 56% had a response of 18 months or longer. Responses ranged from 4.1 to 35.8 or more months.

Safety Profile

AMONG THE patients with SCLC enrolled in KEYNOTE-158 (cohort G, n = 107) and KEYNOTE-028 (cohort C1, n = 24) who were included in the safety analysis, the adverse reactions that occurred were similar to those occurring in patients with other solid tumors who received pembrolizumab as a single agent.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with pembrolizumab, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Based on the severity of the adverse reaction, pembrolizumab should be withheld or discontinued and corticosteroids administered, if appropriate. The drug can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, pembrolizumab can cause fetal harm when administered to a pregnant woman.


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