Durable long-term benefit with first-line nivolumab plus ipilimumab has been reported in patients with advanced NSCLC across PD-L1 expression levels and histologies.
A pooled analysis of data from 1,332 patients from CheckMate trials 227 (Part 1), 817 (cohort A), 568 (Part 1), and 012, out to almost 60 months follow-up in some patients, found a median overall survival of 18.6 months in all patients with a 3-year OS rate of 35%.
“Notably, in CheckMate 012, which had the longest survival follow-up, the 5-year OS rate was 34%,” the study authors said.
The study found the median OS was 15.4, 20.2, 17.1, and 26.0 months in patients with tumour PD-L1 expression level <1%, ≥1%, 1-49%, and ≥50%, respectively. The 3-year OS rates were 30%, 38%, 30%, and 48%.
“Median OS was 15.1 months and 20.0 months in patients with squamous and non-squamous histology, respectively, with 3-year OS rates of 30% and 38%,” it said.
The study, published in Annals of Oncology [link here], found that efficacy outcomes in a subgroup of patients aged ≥75 years were similar to those in the overall pooled population.
Median OS in these older patients – “a patient population of high clinical interest” – was 20.1 months (95% CI, 14.7-26.9), with a 3-year OS rate of 34%.
The safety profile in the pooled population, and in the older patient subgroup, was consistent with previous reports, with no new safety signals.
The study found patients who responded to the dual immunotherapy (CR/PR) at 6 months had longer subsequent OS than non-responders (SD/PD).
“OS was improved in responders versus those with SD/PD at 6 months regardless of tumour PD-L1 expression level,” it said.
A complementary analysis of OS by best overall response also showed that responders to nivolumab plus ipilimumab had better OS than non-responders.
“Data from this large pooled analysis support the clinically meaningful efficacy improvements, such as the durable survival benefit observed previously with nivolumab plus ipilimumab across tumour PD-L1 expression levels and histologies, including in patients with tumour PD-L1 <1% and those with squamous tumour histology (patient populations with typically higher unmet need for durable responses),” the investigators said.
The investigators, including Professor Kenneth O’Byrne from the Princess Alexandra Hospital and the Queensland University of Technology Translational Research Institute, said their findings in advanced NSCLC were consistent with long-term survival observed with dual immunotherapy regimens across other tumour types, including untreated advanced melanoma and advanced renal cell carcinoma.
“This durable benefit may reflect the biological effect of ipilimumab in induction of de novo antitumour T-cell responses and memory T cells,” they said.
They noted a randomised trial was the only way to address the choice of immunotherapy plus chemotherapy versus dual immunotherapy in patients with unmet need, such as those with tumor PD-L1 expression level <1%.