Pembrolizumab offered antitumor activity with durable responses in pretreated patients with advanced small-cell lung cancer (SCLC), according to the results of an analysis of pooled data from the phase 1b KEYNOTE-028 trial and the phase 2 KEYNOTE-158 study presented at the American Association for Cancer Research (AACR) 2019 Annual Meeting, Atlanta, GA. In all, 9 of 16 pembrolizumab-treated cancer survivors experienced responses lasting 18 or more months, without any unexpected toxicities.
SCLC accounts for 15% of diagnosed lung cancers. Smoking is very strongly tied to SCLC—even more so than with other types of lung cancer. Nearly 70% of patients with SCLC have advanced disease at diagnosis, with a 5-year survival rate of 2%.
“Our findings are particularly noteworthy given that data show that historically patients with [SCLC] in the third-line treatment setting have limited survival benefit, with a duration of response of less than 2 months and median survival of around 2 to 3 months,” stated lead author Hyun Cheol Chung, MD, PhD, professor, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. “Our study shows that pembrolizumab monotherapy can provide durable clinical benefit with manageable toxicity in this hard-to-treat patient population.”
In total, 83 eligible patients (median age: 62 years; 64% men; 36% had received ≥ 3 lines of systemic therapy) were included from both trials. Patients from the KEYNOTE-028 study had programmed cell death ligand 1 (PD-L1)–positive tumors, and patients in the KEYNOTE-158 trial did not. The primary endpoint in both studies was objective response rate according to RECIST criteria (version 1.1). Median follow-up was 7.7 months.
The objective response rate was 19.3% (95% CI: 11.4% to 29.4%). Two patients achieved complete responses, and 14 had partial responses. Overall, 14 of 16 responders were PD-L1–positive. The median duration of response, however, was not attained.
The median progression-free survival was 2.0 months (95% CI: 1.9–3.4 months), and median overall survival was 7.7 months (95% CI: 5.2–10.1 months). Finally, 12- and 24-month rates were 16.9% and 13.1% for progression-free survival, respectively, and 34% and 21% for overall survival, respectively.
Among all patients with SCLC, 8% experienced a grade 3 treatment-related adverse event. Three experienced grade 5 treatment-related adverse events, including intestinal ischemia, pneumonia, and encephalopathy.
This study was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co.