Despite no statistically significant benefit in overall survival (OS) observed in the entire population of the Energy-GFPC 06-2015 study performed by the Groupe Fran\u00e7ais de PneumoCancerologie, there was a clinical signal of efficacy of combination treatment with nivolumab and ipilimumab over platinum doublet therapy in elderly patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) 0-1 with a significant OS benefit. The findings are presented by Dr. Herv\u00e9 L\u00e9na of the Centre Hospitalier Universitaire de Rennes in Rennes, France at ASCO 2022 Annual Meeting.<\/p>\n
The authors explained in the study background that a combination of PD1 and CTLA4 monoclonal antibodies have shown superiority over chemotherapy in patients with advanced NSCLC, but data for fit elderly or patients with PS 2 are scarce. The eNErgy compared the combination of nivolumab and ipilimumab to a platinum doublet in elderly or patients with PS 2 and advanced NSCLC. Primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate, and safety.<\/p>\n
Main inclusion criteria were stage IV histologically confirmed NSCLC, age at least 70 years, and PS 0\/1\/2 or age less than 70 years and PS 2, EGFR<\/em>–<\/em>, ALK<\/em>\/ROS1<\/em>–<\/em>negative tumours, who were fit enough to receive a platinum doublet. The main exclusion criteria were active cerebral metastasis or contraindication to combination treatment with nivolumab and ipilimumab.<\/p>\n Patients were randomly selected 1 to 1 and stratified by age \u2265 70 versus < 70 years, PS 0\/1 versus PS 2, and histology squamous versus no-squamous. Nivolumab 240 mg every 2 weeks and ipilimumab 1 mg\/kg every 6 weeks were administrated until progression or unacceptable toxicity. Chemotherapy was planned for 4 cycles with carboplatin (AUC5) and pemetrexed (500 mg\/m2<\/sup> every 3 weeks) or paclitaxel (90 mg\/m2<\/sup> on days 1, 8, 15). In total, 242 patients had to be randomised to detect a treatment effect in hazard ratio (HR) on OS of 0.65 with a 85% power at a 2-sided alpha level of 5%.<\/p>\n A preplanned interim analysis performed after observation of 33% of deaths in 174 randomised patients, showed a risk of futility especially for patients with PS 2 with HR 1.8 (95% confidence interval [CI] 0.99-3.3). This led to a halt in randomisation, but continued follow-up of the 204 patients randomised at the time of the decision.<\/p>\n The final analysis was performed 18 months after the inclusion of the last patient. Most patients were men (71%). Median age was 74 years (range, 51-89). PS 0\/1\/2 was reported in 30%, 37.5%, and 36.6% of patients respectively. Smokers or former smokers were reported in 25.5% and 64.4% of cases. In total, 62% of patients had adenocarcinoma.<\/p>\n Median OS in patients who received the combination of nivolumab and ipilimumab was 14.7 months (95% CI 8.0-19.7) and 9.9 months (95% CI 7.7-12.3) in chemotherapy arm (HR 0.85, 95% CI 0.62-1.16).<\/p>\n The subgroup analyses showed a significant benefit for combination of nivolumab and ipilimumab compared to chemotherapy in elderly patients with PS 0\/1 with median OS of 22.6 months (95% CI 18.1-36) versus 11.8 months (95% CI 8.9-20.5) and p = 0.02. However, in patients with PS 2, median OS in the combination arm with nivolumab and ipilimumab was 2.9 months (1.4-4.8) versus 6.1 months (3.5-10.4) in chemotherapy arm (p = 0.22).<\/p>\n Median PFS was significantly in favour for the combination arm of nivolumab and ipilimumab in the entire population, 5.5 months (2.8-8.7) versus 4.6 months (3.5-5.6) and p = 0.015.<\/p>\n Safety was similar with 31.4% of patients with grade \u2265 3 related serious adverse events in the combination arm of nivolumab and ipilimumab versus 49.5% in chemotherapy arm. Treatment was discontinued due to toxicity in 28.6% of patients in the combination arm of nivolumab and ipilimumab versus 22.3% in chemotherapy arm.<\/p>\n The authors concluded that despite no statistically significant benefit in OS observed in the entire study population, there was a clinical signal of efficacy for combination of nivolumab and ipilimumab over platinum doublet in fit elderly patients with advanced NSCLC.<\/p>\n Lena H, Monnet I, Bylicki O, et al.<\/em> Randomized phase III study of nivolumab and ipilimumab versus carboplatin-based doublet in first-line treatment of PS 2 or elderly (\u2265 70 years) patients with advanced non\u2013small cell lung cancer (Energy-GFPC 06-2015 study)<\/a>. J Clin Oncol<\/em> 2022; 40 (suppl 16; abstr 9011). DOI: 10.1200\/JCO.2022.40.16_suppl.9011<\/p>\nReference<\/h4>\n