Background: The antitumor activity of the anti-PD-1 monoclonal antibody pembrolizumab in patients with advanced SCLC has been evaluated in the Phase Ib basket study KEYNOTE-028 (KN028; NCT02054806) and in the Phase II basket study KEYNOTE-158 (KN158; NCT02628067). We present outcomes for patients enrolled in KN028 and KN158 who were receiving pembrolizumab after ≥2 lines of prior therapy.

Methods: Eligible patients had histologically/cytologically confirmed incurable advanced SCLC, measurable disease per RECIST 1.1, ECOG PS of 0/1, had experienced progression/failure on standard therapy, and were immunotherapy-naive; patients included in this analysis had received ≥2 lines of systemic therapy. Patients in KN028 were required to have PD-L1-positive tumors (membranous PD-L1 expression in ≥1% of tumor and associated inflammatory cells or positive staining in stroma); tumor PD-L1 expression was not required in KN158. Radiographic imaging was performed Q8W for 6 mo (KN028) or Q9W for 1 y (KN158), and Q12W thereafter. Pembrolizumab (10 mg/kg Q2W [KN028] or 200 mg Q3W [KN158]) was administered for 2 y or until disease progression or intolerable toxicity. The primary endpoint in both studies was objective response rate (ORR) assessed per RECIST 1.1. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were secondary endpoints and estimated using the Kaplan-Meier method. For this analysis, assessment of response was by independent central review.

Results: Of 131 SCLC pts included in both trials, 83 were eligible for efficacy analyses (KN158, n=64; KN028, n=19). Median age was 62 (range, 24–84) y, 64% were men, and 36% had received ≥3 lines of systemic therapy. As of the data cutoff date, median follow-up was 7.7 (range, 0.5–48.7) mo. The ORR was 19.3% (95% CI, 11.4-29.4). Two patients had a complete response and 14 had a partial response per independent central review; 14 of 16 responders were PD-L1-positive. Median DOR was not reached (range, 4.1-35.8 [ongoing] mo). 9 of 16 responders (61% per Kaplan-Meier estimate) had response lasting ≥18 mo. Median PFS was 2.0 (95% CI, 1.9-3.4) mo and median OS was 7.7 (95% CI, 5.2-10.1) mo. 12- and 24-month rates were 16.9% and 13.1% for PFS, and 34% and 21% for OS. Among all SCLC patients in KN028 and KN158 irrespective of prior therapies (N=131), 8% had a grade 3 treatment-related AE (no grade 4 treatment-related AEs). 3 patients had grade 5 treatment-related AEs (intestinal ischemia, pneumonia, encephalopathy). 21% experienced an immune-mediated AE or infusion reaction.

Conclusions: Pembrolizumab demonstrated promising antitumor activity in patients with advanced SCLC who had received ≥2 lines of prior therapy. Responses were durable, with the majority of patients estimated to have a response duration of at least 18 mo. No unexpected toxicities from pembrolizumab were observed.

Citation Format: Hyun Cheol Chung, Sarina A. Piha-Paul, Jose Lopez-Martin, Jan H.M. Schellens, Steven Kao, Wilson H. Miller Jr., Jean-Pierre Delord, Bo Gao, David Planchard, Maya Gottfried, Alona Zer, Shadia I. Jalal, Nicolas Penel, Janice M. Mehnert, Ignacio Matos, Jaafar Bennouna, Dong-Wan Kim, Lei Xu, Suba Krishnan, Kevin Norwood, Patrick A. Ott. Pembrolizumab after two or more lines of prior therapy in patients with advanced small-cell lung cancer (SCLC): Results from the KEYNOTE-028 and KEYNOTE-158 studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT073.