Keytruda® Approved for Small Cell Lung Cancer

The Food and Drug Administration (FDA) has granted approval for Keytruda® (pembrolizumab) to treat metastatic small cell lung cancer (SCLC).

Pembrolizumab was approved as a third-line therapy for SCLC patients who still present disease progression despite current or past platinum-based chemo and at least one other prior line of therapy, according to the FDA.

Keytruda is manufactured by Merck.

“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 press release. “We look forward to continuing to advance important clinical research in small cell lung cancer.”

“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. “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.”

Two Studies Evaluate Pembrolizumab

The FDA’s latest approval follows the results of two trials—KEYNOTE-158 and KEYNOTE-028.

KEYNOTE-158 was a phase II study investigating the use of pembrolizumab in patients with previously treated advanced cervical cancer. A total of 98 patients (mean age, 46 years; range, 24–75 years) were treated with pembrolizumab 200 mg every three weeks for two years, if they presented progression or intolerable toxicity, or until a patient or physician decided to stop treatment. For the first year of treatment, patients underwent tumor imaging every nine weeks, and subsequently every 12 weeks. The primary outcome was objective response rate (ORR) per the Response Evaluation Criteria in Solid Tumors (version 1.1), and the secondary outcome was safety. Patients were followed for a median 10.2 months (range, 0.6–22.7 months).

There were 12 responses—three complete and nine partial; ORR was 12.2% (95% confidence interval [CI] 6.5–20.4%). All 12 of the patients with responses had PD-L1-positive tumors for an ORR of 14.6% (95% CI 7.8–24.2%), of which 14.3% (95% CI 7.4–24.1%) were in patients who had received at least one line of chemotherapy for recurrent or metastatic disease. Adverse events occurred in 65.3% of patients, the most prevalent of which included hypothyroidism (10.2%), decreased appetite (9.2%), and fatigue (9.2%).

KEYNOTE-028 evaluated patients with PD-L1-positive advanced solid tumors. The nonrandomized, phase Ib trial included 475 patients who received pembrolizumab 10 mg/kg every two weeks for two years or until progression or toxicity. The primary endpoint in this trial was also ORR, with secondary outcomes including safety, progression-free survival (PFS), and overall survival (OS).

Outcomes varied significantly based on cancer type. ORRs ranged from 0% (95% CI 0.0–14.2%) in pancreatic cancer to 33% (95% CI 15.6–55.3%) in SCLC. Similarly, median PFS varied from 1.7 months (95% CI 1.5–2.9 months) in pancreatic cancer to 6.8 months (95% CI 1.9–14.1 months) in thyroid cancer, and median OS was 3.9 months (95% CI 2.8–5.5 months) in vulvar tumors versus 21.1 months (95% CI 9.1–22.4 months) in carcinoid tumors. Safety outcomes were consistent with previous pembrolizumab studies.