In the longest follow-up on single-agent nivolumab to date, 5-year overall survival (OS) was 16% in patients with advanced non–small cell lung cancer (NSCLC) in updated results from a phase 1b dose-ranging study (CA209-003). This represents a quadrupling of 5-year OS with standard platinum doublets, which is about 4% for metastatic NSCLC.
That’s the good news; the not-so-good news is that no biomarkers for response or survival could be identified in this study.
“This is the first report of long-term survival rate in patients with metastatic NSCLC treated with an immune checkpoint inhibitor. Our study results show that for a small subset of patients, immunotherapy can work for a very long time,” stated lead author Julie Brahmer, MD, associate professor of oncology at the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins Medicine in Baltimore, MD.
CA209-003 was a phase 1b, open-label, multicenter, dose-escalation study of nivolumab that enrolled 129 patients with advanced or recurrent NSCLC and any level of PD-L1 expression, including patients previously treated with 1 to 5 prior systemic therapies. Three dosing cohorts (1, 3, and 10 mg/kg) received nivolumab every 2 weeks for up to 96 weeks. Dr Brahmer presented pooled data for all 3 dosing cohorts.
The estimated rate of 5-year OS was 16%. Median OS was 9.9 months at a minimum of 58 months of follow-up. Five-year survival rates were consistent for squamous (16%) and nonsquamous (15%) histology. In 68 of 129 patients with evaluable PD-L1 expression (53% of patients), 5-year survival rates increased in a linear fashion with increasing rates of PD-L1 expression. Five-year survival rates were 20% in those with PD-L1 <1%, 23% in those with PD-L1 >1%, and 43% in those with PD-L1 >50%. Among patients with unknown PD-L1 expression levels, estimated 5-year OS was 10%.
Of 16 patients who survived for at least 5 years, 9 were male and 12 were current smokers at trial enrollment. Twelve patients had a partial response, 2 had stable disease, and 2 had progressive disease.
Eight patients completed 2 years of treatment with no side effects, and 4 discontinued treatment early because of side effects. None of these 12 patients required further treatment and had no evidence of disease progression at their last follow-up visit.
No pattern was observed for clinical and tumor characteristics that could predict survival in this study.
“PD-L1 status was not clearly associated with long-term survival in this small group of patients. We want to better understand which patients can stop treatment at 2 years and which of them need to continue treatment beyond 2 years,” she said. “Based on these data, I think we can shorten the amount of time patients are treated. Ongoing trials are looking to compare different durations of therapy, such as CheckMate 103,” Dr Brahmer said.
“We can safely say NSCLC patients do not need indefinite treatment. We are continuing to look for biomarkers. In this trial, no characteristic stands out to identify long-term survivors,” she concluded.
Nivolumab is approved by the FDA as second-line treatment for NSCLC.
