CHICAGO — Nivolumab with or without ipilimumab induced durable objective responses and was associated with manageable safety profiles in patients with previously treated advanced small cell lung cancer (SCLC), according to a study presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.1
“The majority of patients with SCLC respond to first-line chemotherapy, but everyone relapses,” said lead investigator Scott J. Antonia, MD, department chair of the thoracic oncology department at the Moffitt Cancer Center in Tampa, FL. “Outcomes with second-line treatments are poor.”
Because patients with advanced SCLC who are relapsed or are refractory to first-line platinum-based chemotherapy have limited treatment options, researchers sought to evaluate the efficacy and safety of nivolumab with or without ipilimumab in this patient population.
For the study, researchers enrolled 216 patients with progressive disease after 1 or more platinum-based chemotherapy regimens, regardless of platinum sensitivity or tumor programmed cell death ligand-1 (PD-L1) expression. Patients received nivolumab 3 mg/kg IV every 2 weeks, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg IV every 3 weeks for 4 cycles, or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 cycles. All patients then received nivolumab 3 mg/kg alone every 2 weeks.
Among all patients, approximately half had received at least 2 prior regimens, the vast majority were current/former smokers, and most had a PD-L1 expression level less than 1%.
Results showed that the objective response rate for the nivolumab monotherapy group was 10%, 23% for the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group, and 19% for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group. Two percent of patients in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort achieved complete responses.
“Tumor responses were observed regardless of platinum sensitivity or tumor PD-L1 expression,” Dr Antonia added.
Researchers found that median overall survival was 4.4 months with single-agent nivolumab, 7.7 months with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 6.0 months with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. The 1-year overall survival rates were 33%, 43%, and 35%, respectively.
“Although preliminary, the survival results were encouraging,” Dr Antonia noted.
In regard to safety, grade 3 or 4 treatment-related adverse events were reported in 13% of patients who received nivolumab alone, in 30% of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and in 19% of patients who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. Treatment-related adverse events resulted in treatment discontinuation in 6%, 11%, and 7%, respectively.
“Immune-related adverse events were managed using established safety guidelines,” Dr Antonia said.
Of note, 2 patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related myasthenia gravis and worsening of renal failure, respectively, and 1 patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonitis.
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Ultimately, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg was selected for further study in a phase 3 trial and the CheckMate 032 trial will be expanded to include 250 patients.
Nivolumab monotherapy is also being compared with chemotherapy (topotecan or amrubicin) in relapsed SCLC in the CheckMate 331 trial, as well as with nivolumab plus ipilimumab or placebo as consolidation/maintenance after platinum-based first-line therapy in patients with extensive-stage SCLC.
- Antonia SJ, Lopez-Martin JA, Bendell JC, et al. Checkmate 032: Nivolumab (N) alone or in combination with ipilimumab (I) for the treatment of recurrent small cell lung cancer (SCLC). J Clin Oncol. 2016; 34 (suppl; abstr 100).