Treatment with nivolumab (Opdivo) did not improve response rates or survival over standard chemotherapy in patients with metastatic small cell lung cancer (SCLC) who relapsed following first-line treatment, according to findings presented by Reck et al at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2018 (Abstract LBA3).
Study author Martin Reck, MD, PhD, of the LungenClinic Grosshansdorf, noted that although patients with SCLC often show high initial response rates, most patients will relapse soon after first-line treatment. These relapsing patients have few treatment options, leaving them with a poor prognosis.
Dr. Reck and colleagues conducted the CheckMate 331 trial evaluating nivolumab, which has been approved in the U.S. for treatment of patients with SCLC and progression after platinum-based chemotherapy and one or more other lines of treatment.
CheckMate 331 was a global, open-label, phase III trial comparing nivolumab to chemotherapy. The trial enrolled 569 patients with limited or extensive relapsed metastatic SCLC who progressed after first-line platinum-based chemotherapy. The patients were randomly assigned 1:1, with 282 patients receiving nivolumab and 285 receiving chemotherapy with topotecan or amrubicin, according to local approval. The patients were stratified by platinum sensitivity (90 days) and the presence of central nervous system metastases. Both treatments were continued until progression, or clinical benefit was no longer observed with nivolumab, or until unacceptable toxicity occurred. Overall survival (OS) with nivolumab vs chemotherapy served as the primary endpoint.
After a minimum follow-up of 15.8 months, 225 (79%) OS events occurred with nivolumab compared to 245 (86%) with chemotherapy.
No statistically significant improvement in OS was seen with nivolumab compared to chemotherapy; median OS was 7.5 months vs 8.4 months with nivolumab vs chemotherapy, respectively (hazard ratio [HR] = 0.86; 95% confidence interval [CI] = 0.72–1.04). However, the OS curves showed delayed separation after month 12; the 1-year OS rates were 37% with nivolumab vs 34% with chemotherapy.
With the respective treatments, median progression-free survival (PFS) was median 1.5 vs 3.8 months (HR = 1.41; 95% CI = 1.18–1.69) and the 1-year PFS rates were 11% vs 10%.
The objective response rates were 39% vs 47%, and the duration of response in responding patients was median 8.3 (95% CI = 7.0–12.6) months vs 4.5 (95% CI = 4.4–5.8) months with nivolumab vs chemotherapy, respectively,
In patients with platinum-resistant SCLC, the HR for OS with nivolumab vs chemotherapy was 0.71 (95% CI = 0.54–0.94).
The safety profile was improved with nivolumab compared to chemotherapy. All-grade treatment-related adverse events (TRAE) occurred in 55% vs 90%, and grade 3–4 TRAE occurred in 4% vs 73% of nivolumab- vs chemotherapy-treated patients. Two treatment-related deaths occurred with nivolumab, and 3 deaths occurred that were chemotherapy-related.
The study authors concluded, “CheckMate 331 did not meet the primary endpoint of OS for nivolumab vs chemotherapy in second-line SCLC. However, late separation of curves and potential activity in the platinum-refractory setting suggests possible long-term benefit for some patients. There were no new safety signals, with lower adverse event rates observed with nivolumab.”
Disclosure: The study authors’ full disclosures can be found at academic.oup.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.