FDA Approves Pembrolizumab for SCLC Treatment

The Food and Drug Administration (FDA) approved the PD-1 inhibitor, pembrolizumab (Keytruda), for the treatment of patients with advanced small cell lung cancer (SCLC) who experienced disease progression after 2 or more prior lines of therapy. This is the first indication for the drug in the SCLC setting.

Continued approval for this indication may be contingent upon verification of clinical benefit in the confirmatory trials.

The approval is based off findings from two studies — the phase II KETNOTE-158 and the phase Ib KEYNOTE-028 – where the immunotherapy agent elicited a 19% overall response rate (ORR), 2% complete response (CR) rate and 17% partial response rate.

“Keytruda is already an established treatment option for non-small cell lung cancer, and today’s approval in small cell lung cancer demonstrates our commitment to bringing forward new treatment options for patients with advanced, difficult-to-treat cancers,” said Jonathan Cheng, MD, vice president, oncology clinical research, Merck Research Laboratories, in a statement. “We look forward to continuing to advance important clinical research in small cell lung cancer.”

KEYNOTE-158 is a basket study involving patients with 10 different tumor types, plus those with microsatellite instability-high (MSI-H) cancers, including patients with SCLC. Participants were given 200 mg of pembrolizumab intravenously (IV) every 3 weeks for 2 years or until disease progression, unacceptable toxicity, or study withdrawal. In the SCLC cohort, patients needed to have unresectable and/or metastatic disease, progression on or intolerance to standard therapy, an ECOG performance status of 0 or 1, at least 1 measurable lesions, evaluable tumor sample for biomarker assessments, and no autoimmune disease or noninfectious pneumonitis.

KEYNOTE-028 is a nonrandomized, multi-arm trial where the safety and efficacy of pembrolizumab was evaluated in patients who had advanced solid tumors. They received 10mg/kg of pembrolizumab every 2 weeks for 24 months until progression, intolerable toxicity, physician decision to discontinue, or withdrawal of consent.

Of the 16 patients who responded to pembrolizumab, 94% had a duration of response (DOR) of 6 months or longer; 63% had a DOR lasting 12 months or longer; and 56% had a DOR lasting 18 months or longer.

Severe immune-related adverse events (AEs) from pembrolizumab treatment can include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, renal dysfunction, severe skin reactions, solid organ transplant rejection, and allogenic hematopoietic stem cell transplant complications. The PD-1 inhibitor can also cause fetal harm when administered to pregnant women.

“Small cell lung cancer, which accounts for 10 to 15% of all lung cancers, is often diagnosed at an advanced stage where the prognosis is very poor and there have historically been limited treatment options,” said Patrick Ott, MD, PhD, clinical director, Center for Immuno-Oncology, Dana-Farber Cancer Institute, in a statement. “The approval of Keytruda in small cell lung cancer provides an additional treatment option for patients based on the clinical response rates from KEYNOTE-158 and KEYNOTE-028.”