COPENHAGEN, Denmark — Nivolumab did not significantly extend PFS compared with investigator’s choice of platinum-doublet chemotherapy in patients with stage IV or recurrent PD-L1–positive non–small cell lung cancer, according to results of the phase 3 CheckMate 026 trial presented at the European Society for Medical Oncology Congress.
“Nivolumab [Opdivo, Bristol-Myers Squibb] has replaced the standard of care in previously treated metastatic NSCLC patients regardless of PD-L1 expression, and this study aimed to answer an important clinical question of whether this PD-1 inhibitor could provide superior benefit over chemotherapy in a broad patient population in the first-line setting,” Mark Socinski, MD, executive medical director of Florida Hospital Cancer Institute, said in a company-issued press release. “These findings provide additional understanding of the role of PD-1 monotherapy in treatment-naive patients and confirm there is still a significant opportunity for improving outcomes for the majority of these patients.”
In the phase 1 CheckMate 012 study, nivolumab showed promising activity for the monotherapy treatment of treatment-naive advanced NSCLC.
Based on those results, Socinski and colleagues conducted a phase 3 study in 541 patients with previously untreated stage IV or recurrent NSCLC who had an ECOG performance status of 0 to 1 and were PD-L1 positive.
Researchers randomly assigned patients 1:1 to receive 3 mg/kg IV nivolumab every 2 weeks, or histology-based investigator’s choice of platinum-based doublet chemotherapy every 3 weeks. Patients received treatment for up to six cycles or until disease progression or unacceptable toxicity, and those assigned the chemotherapy arm were allowed to crossover to the nivolumab arm upon progression.
PFS assessed by an independent radiology review committee in patients with 5% or greater PD-L1 tumor expression at randomization served as the study’s primary endpoint.
Overall, 423 of the enrolled patients had 5% or greater PD-L1 expression. Among these patients, treatment with nivolumab did not improve median PFS (4.2 months vs. 5.9 months; HR = 1.15; 95% CI, 0.91-1.45).
“There are a number of possible reasons for the disappointing PFS results,” Socinski said in a press release issued by European Society for Medical Oncology. “Regarding OS, there was a high rate of crossover to immunotherapy on the chemotherapy arm. OS in the chemotherapy arm was better than historical standards, which could be due to the fact that it had a greater proportion of women and Asian patients. We are conducting further analyses to evaluate these results.”
Median OS was 14.4 months for nivolumab vs. 13.2 months for chemotherapy (HR 1.02, 95% CI 0.8–1.3).
Fewer patients who received nivolumab experienced any-grade (71% vs. 19%) or grade 3 or grade 4 (18% vs. 51%) toxicity.
“Platinum-based chemotherapy is the standard first-line treatment because it makes patients live longer and palliates symptoms,” Socinski said. “If we are going to replace it with immunotherapy, we need to be confident that we are identifying the patients who will derive greater benefit.
“Combination immunotherapies may increase the proportion of patients who benefit in the first line,” Socinski added. “The phase 3 CheckMate 227 trial is investigating treatment with nivolumab plus ipilimumab [Yervoy, Bristol-Myers Squibb] in the first-line setting relative to standard chemotherapy.” – by Alexandra Todak
Socinski M, et al. Abstract LBA7_PR. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.
Disclosure: The study was funded by Bristol-Myers Squibb. Socinski reports no relevant financial disclosures. Please see the abstract for a list of the researchers’ relevant financial disclosures.