The programmed death 1 (PD-1) inhibitor pembrolizumab offers promising antitumor activity and a safety profile consistent with earlier research in heavily pretreated patients with programmed death ligand 1 (PD-L1)–expressing extensive-stage small-cell lung cancer (SCLC), according to results of a phase I study.
“Although response rates of 50% to 80% are achieved in first-line treatment [of SCLC] with a platinum and etoposide chemotherapy doublet, progression occurs universally, and outcomes with second-line treatments are poor,” wrote study authors led by Patrick A. Ott, MD, PhD, of Dana-Farber Cancer Institute in Boston. Tumors that upregulate PD-L1 can evade T-cell–mediated destruction, and previous work has shown that blocking PD-1 can enhance that immune-mediated cell death.
The open-label phase Ib KEYNOTE-028 study tested pembrolizumab in 24 patients with extensive-stage SCLC who were PD-L1–positive by immunohistochemistry. Patients had a median age of 60.5 years; all patients had previously received chemotherapy, and half of the cohort had received two prior lines of treatment. The results of the study were published in the Journal of Clinical Oncology.
The confirmed objective response rate was 33.3%, with 1 patient achieving a complete response (4.2%) and 7 patients with partial responses (29.2%). One patient (4.2%) had stable disease for less than 6 months, and 13 patients (54.2%) had disease progression as their best overall response. The median time to response was 2.0 months, and the median duration of response was 19.4 months.
The median progression-free survival (PFS) in the study was 1.9 months, with a 6-month PFS rate of 28.6% and a 12-month rate of 23.8%. The median overall survival was 9.7 months, and the 6- and 12-month rates were 66.0% and 37.7%, respectively.
All patients experienced at least one adverse event during the study. Most patients (66.7%) experienced treatment-related events, the most common of which included arthralgia, asthenia, and rash. Grade 3–5 adverse events were seen in 8 patients (33.3%), and 2 of those were deemed to be related to treatment. One patient had grade 3 bilirubin elevation, and another had asthenia, grade 5 colitis, and intestinal ischemia.
“Pembrolizumab showed clinically meaningful antitumor activity and overall was well tolerated,” the authors wrote. “The safety was consistent with the reported safety profile in other tumor types.” They noted that based on the clinical and safety signals from this trial, multiple further studies have been initiated to examine biomarkers in this setting and to test the agent in frontline and maintenance settings, and in combination with other therapies.