SUMMARY: The FDA on June 17, 2019 granted accelerated approval to KEYTRUDA® (Pembrolizumab) 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. The American Cancer Society estimates that for 2019 about 228,150 new cases of lung cancer will be diagnosed and about 142,670 patients will die of the disease. Lung cancer is the leading cause of cancer-related mortality in the United States. Small cell lung cancer (SCLC) accounts for approximately 13-15% of all lung cancers, and is aggressive. Patients with SCLC are often treated with platinum based chemotherapy as first-line treatment, and the tumor response rates are as high as 60-80%. However, only 20% of patients with Limited Stage SCLC are cured, and majority of the patients relapse within months of completing initial therapy. Patients often receive HYCAMTIN® (Topotecan) for recurrent or progressive SCLC (second-line treatment) and after failure on second-line therapy, treatment options are limited. The 5 year survival rate for Extensive Stage SCLC is less than 5%, with a median survival of 9-10 months from the time of diagnosis.
KEYTRUDA® is a fully humanized, Immunoglobulin G4, anti-PD-1, monoclonal antibody, that binds to the PD-1 receptor and blocks its interaction with ligands PD-L1 and PD-L2. It thereby reverses the PD-1 pathway-mediated inhibition of the immune response and unleashes the tumor-specific effector T cells.
The present FDA approval was based on pooled data from two Basket studies, KEYNOTE-158 (cohort G) and KEYNOTE-028 (cohort C1), which are two multicenter, multi-cohort, non-randomized, open-label trials, evaluating KEYTRUDA® in patients with SCLC, who had disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. In Basket trials, patients with different tumor histologies receive a single treatment and have a single biomarker. Among the 83 patients evaluated in both these studies for efficacy, 64% received two prior lines of therapy and 36% received three or more lines of therapy; 60% received prior thoracic radiation therapy; 51% received prior radiation therapy to the brain. Patients in the KEYNOTE-028 were required to have tumors expressing PD-L1, whereas PD-L1 positivity was not required for KEYNOTE-158. Patients in the KEYNOTE-028 study received KEYTRUDA® 10 mg/kg IV every 2 weeks (N=19), whereas those in KEYNOTE-158 received KEYTRUDA® 200 mg IV every 3 weeks (N=64). Treatment was continued until documented disease progression, unacceptable toxicity, or a maximum of 24 months. The major efficacy outcome measures included Objective Response Rate (ORR) and Duration of Response (DOR).
Treatment with KEYTRUDA® resulted in an Overall Response Rate of 19%, with a Complete Response Rate of 2% and a Partial Response Rate of 17%. Of the responding patients, 94% had a Duration of Response (DOR) of 6 months or longer, 63% had a DOR of 12 months or longer, and 56% had a DOR of 18 months or longer. Responses ranged from 4.1 to over 35.8 months. Adverse Events were similar to those occurring in patients with other solid tumors who received KEYTRUDA® as a single agent and the common adverse reactions included fatigue, decreased appetite, cough, nausea and constipation.
It was concluded that this new indication marks the first FDA approval for KEYTRUDA® in Small Cell Lung Cancer, and provides an additional treatment option for patients with advanced stage disease, based on clinical response rates. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-metastatic-small-cell-lung-cancer
