Keytruda Approved for Patients with Previously Treated Metastatic Small-Cell Lung Cancer

Web Exclusives - FDA Updates, In the News
Yvette Florio Lane

Lung cancer is the second most frequently diagnosed malignancy in both men and women (following prostate and breast cancer, respectively), and the leading cause of cancer deaths overall. Non–small-cell lung cancer (NSCLC) is the most common type, with the more aggressive small-cell lung cancer (SCLC) making up approximately 10% to 15% of cases.

On June 17, 2019, the US Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Keytruda; Merck) for the treatment of patients with metastatic SCLC who have progressive disease following platinum-based chemotherapy and at least 1 other previous line of therapy. This approval marks the first time the immunotherapeutic agent has been indicated for the treatment of patients with SCLC.

Pembrolizumab, an anti–PD-1 therapy, was previously approved as monotherapy for first-line treatment of patients with metastatic NSCLC whose tumors had a PD-L1 tumor proportion score (TPS) of ≥50%. In April 2019, the FDA expanded pembrolizumab’s indication to include the first-line treatment of patients with unresectable stage III NSCLC and for patients who are ineligible to undergo definitive chemoradiation, as well as those with metastatic disease. Patients who are eligible to receive pembrolizumab must have tumors that express PD-L1, a TPS of ≥1% as determined by an FDA-approved test, and no EGFR or ALK mutations.

KEYNOTE-158 and KEYNOTE-028 Clinical Trials

Accelerated approval was based on observed tumor response rate and durability of response in 83 patients enrolled in 1 of 2 multicenter, multicohort, nonrandomized, open-label clinical trials (KEYNOTE-158 or KEYNOTE-028).

Patients with SCLC who had disease progression on or after 2 or more previous lines of therapy received either pembrolizumab 200 mg intravenously every 3 weeks (N = 64) or 10 mg/kg intravenously every 2 weeks (N = 19). Treatment continued until documented disease progression, unacceptable toxicity, or a maximum of 24 months.

Major efficacy outcome measures were objective response rate (ORR) and duration of response (modified RECIST v1.1). As assessed by blinded independent central review, the ORR was 19% and the complete response rate was 2%. Of the 16 responding patients, durable responses of ≥6 months were achieved in 94% of patients, ≥12 months in 63%, and ≥18 months in 56%.

Adverse Reactions

The most common adverse reactions in ≥20% of patients who received single-agent pembrolizumab for previously treated SCLC included fatigue, decreased appetite, cough, nausea, and constipation. Adverse reactions in 9% of patients led to discontinuation of pembrolizumab and 25% of patients had at least 1 dose withheld. Serious adverse reactions occurred in 31% of patients. Pneumonia and pleural effusion were the most frequently occurring (≥2%) serious adverse reactions.

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TOP - November 2019, Vol 12, No 4 published on November 7, 2019 in FDA Updates
Last modified: July 11, 2019