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Abstract CT073: 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

2019; American Association for Cancer Research; Volume: 79; Issue: 13_Supplement Linguagem: Inglês

10.1158/1538-7445.am2019-ct073

1538-7445

Hyun Cheol Chung, Sarina A. Piha‐Paul, José A. López-Martín, Jan H.M. Schellens, Steven Kao, Wilson H. Miller, 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,

Cancer Immunotherapy and Biomarkers

Abstract 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.