Pembrolizumab + amrubicin in patients with relapsed small-cell lung cancer: multi-institutional, single-arm phase II study

ABSTRACT Introduction In relapsed small-cell lung cancer (SCLC) patients, amrubicin (AMR) is the current standard treatment in Japan. However, its efficacy is not satisfactory and prognosis is poor. Preclinical study suggested anthracycline agent might induce immunogenic cell death and work synergistically with immune checkpoint inhibitors (ICIs). Patients and Methods Patients with relapsed small-cell lung cancer who relapsed after completion of platinum-containing regimen were registered. Patients were treated with pembrolizumab (Pembro, 200 mg, flat dose on day 1, every three weeks for two years) plus AMR (40 mg/m2 on days 1 to 3, every three weeks until progression). Primary endpoint was overall response rate (ORR). Secondary endpoints consisted of progression-free survival (PFS), overall survival (OS) and safety. Based on the hypothesis that this treatment will improve ORR from 20 to 40% (0.1 of one-sided α and power of 0.8), 25 patients are required (Trial identifier: NCT03253068). Results Between November 2017 and October 2019, 25 patients were enrolled. Most participants (88%) relapsed within 90 days after platinum-containing therapy and all patients were ICI-naive. ORR, the primary endpoint, was 52.0% (95%CI: 31.3 to 72.2%). Median PFS was 4.0 months (95%CI: 2.8 to 7.0 months) and PFS rate at one year was 14.4%. Median OS was 10.6 months (95%CI: 7.3 to 21.3 months). Common adverse events ≥ Gr 3 were neutropenia (64%), leukopenia (40%) and febrile neutropenia (16%). No treatment-related deaths occurred. Conclusion Among patients with relapsed SCLC, Pembro plus AMR was effective and tolerable.