FDA Approves Pembrolizumab for Metastatic Small Cell Lung Cancer
On June 17, 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Keytruda®) 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.
Efficacy was investigated in 83 patients with SCLC who had disease progression on or after two or more prior lines of therapy enrolled in one of two multicenter, multi-cohort, non-randomized, open label trials: KEYNOTE-158 (NCT02628067) Cohort G or KEYNOTE-028 (NCT02054806) Cohort C1. Patients received either pembrolizumab 200 mg via IV every three weeks (n = 64) or 10 mg/kg via IV every two weeks (n=19). Treatment continued until documented disease progression, unacceptable toxicity, or a maximum of 24 months.
The main efficacy outcome measures were overall response rate (ORR) and duration of response (modified RECIST v1.1) assessed by blinded independent central review. The ORR was 19% (95% CI: 11, 29); the complete response rate was 2%. Responses were durable for six months or longer in 94%, 12 months or longer in 63%, and 18 months or longer in 56% of the 16 responding patients.
Adverse reactions in patients who received single-agent pembrolizumab for previously treated SCLC were similar to those occurring in patients with other solid tumors who received pembrolizumab. Common adverse reactions reported in at least 20% of patients include fatigue, decreased appetite, cough, nausea and constipation. Pembrolizumab was discontinued for adverse reactions in 9% of patients and 25% had at least one dose withheld for adverse reactions. Serious adverse reactions occurred in 31%. The most frequent (≥ 2%) serious adverse reactions were pneumonia and pleural effusion.
The recommended pembrolizumab dose for SCLC is 200 mg administered as an IV infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab was granted orphan drug designation for SCLC in October 3, 2017. FDA granted this application priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Project Facilitate: The Oncology Center of Excellence program for Expanded Access—For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 1-800-FDA-1088.
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