Third-Line Nivolumab Monotherapy in Recurrent SCLC: CheckMate 032

Abstract

Introduction: For patients with recurrent SCLC, topotecan remains the only approved second-line treatment, and the outcomes are poor. CheckMate 032 is a phase 1/2, multicenter, open-label study of nivolumab or nivolumab plus ipilimumab in SCLC or other advanced/metastatic solid tumors previously treated with one or more platinum-based chemotherapies. We report results of third-or later-line nivolumab monotherapy treatment in SCLC.Methods: In this analysis, patients with limited-stage or extensive-stage SCLC and disease progression after two or more chemotherapy regimens received nivolumab monotherapy, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety.Results: Between December 4, 2013, and November 30, 2016, 109 patients began receiving third-or later-line nivolumab monotherapy. At a median follow-up of 28.3 months (from first dose to database lock), the objective response rate was 11.9% (95% confidence interval: 6.5-19.5) with a median duration of response of 17.9 months (range 3.0-42.1). At 6 months, 17.2% of patients were progression-free. The 12-month and 18-month overall survival rates were 28.3% and 20.0%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 11.9% of patients. Three patients (2.8%) discontinued because of treatment-related adverse events.Conclusions: Nivolumab monotherapy provided durable responses and was well tolerated as a third-or later-line treatment for recurrent SCLC. These results suggest that nivolumab monotherapy is an effective third-or later-line treatment for this patient population. Ó 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

“…Results from clinical studies investigating the role of anti-PD-1/PD-L1 drugs in secondor further-line setting were conflicting so far, particularly when used as single-agent. [31][32][33][34][35][36] In the recently reported Phase 3 CheckMate-331 trial of nivolumab, a human IgG4 monoclonal antibody against PD-1, 569 SCLC patients relapsed on or following platinum-based chemotherapy were randomised (1:1) to receive either nivolumab (N = 284) or standard second-line chemotherapy (topotecan or amrubicin, N = 285). 37 Results of this study showed that, after 7.0-7.6 months of median follow-up, nivolumab did not yield a significant survival improvement (primary endpoint) compared to the standard chemotherapy arm (7.5 months [95% CI 5.6-9.2] versus 8.4 months [95% CI 7.0-10.0], p = 0.11).…”

Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort

“…11 Furthermore, the efficacy of nivolumab monotherapy in this analysis was similar to that from the pooled nonrandomized and randomized cohorts of patients who received third-or later-line nivolumab monotherapy in CheckMate 032 (ORR, 11.6% versus 11.9%; median DOR, 15.8 months versus 17.9 months; 12-month OS rate, 30.5% versus 28.3%). 12 The combination of nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) significantly improved the primary endpoint of ORR compared with nivolumab monotherapy; however, the combination was associated with increased toxicity, and the higher response rate did not translate into longer PFS or OS. Additionally, no significant benefit in OS was observed with nivolumab plus ipilimumab versus nivolumab in any March 2020 Nivolumabipilimumab in recurrent SCLC patient subgroups analyzed, although the 24-month OS rates were clinically meaningful (w18%) in both groups.…”

“…The safety profile for nivolumab monotherapy was consistent with that seen in pooled data from the randomized and nonrandomized SCLC cohorts. 12 The doses of nivolumab and ipilimumab administered to patients with SCLC in the combination group of the randomized cohort (nivolumab, 1 mg/kg every 2 weeks; ipilimumab, 3 mg/kg every 3 weeks) differ from those being explored in patients with NSCLC (nivolumab, 3 mg/kg every 2 weeks; ipilimumab, 1 mg/kg every 6 weeks) [15][16][17] ; however, the safety profiles of both monotherapy and combination treatment were in accordance with those observed in other tumor types, 2 and no new safety signals were identified. Data are based on a database lock of November 6, 2017, and include events reported from the time of the first dose of study drug to 30 days after the last dose.…”

“…11 In addition to these analyses of the randomized cohort, pooled efficacy and safety data for third-line or later nivolumab monotherapy from the nonrandomized and randomized cohorts have been reported with a minimum follow-up of 11.9 months. 12 Based on these data, the FDA approved nivolumab monotherapy for the treatment of metastatic SCLC with progression after platinum-based chemotherapy and at least one other line of therapy. 2 This paper presents updated efficacy and safety data from the randomized cohort of patients with SCLC, including long-term OS data.…”

Landscape and Future Perspectives of Immunotherapy in Neuroendocrine Neoplasia

“…The most common Grade 3-4 AEs were increased serum lipase levels and diarrhea. A subsequent analysis, evaluating the efficacy of nivolumab in SCLC patients who received nivolumab monotherapy as a third-line treatment, showed an ORR of 11.9%, with a median DOR of 17.9 months (range 3.0-42.1 months) [69]. Based on these results, the FDA approved nivolumab monotherapy in the third-line treatment of SCLC.…”