Longest Follow-Up in Patients with NSCLC Who Responded to Immunotherapy with Nivolumab
Washington, DC—In the longest follow-up on single-agent nivolumab (Opdivo) to date, 5-year overall survival was 16% in patients with advanced non–small-cell lung cancer (NSCLC) in the updated results of a phase 1b dose-ranging study (CA209-003). This represents a quadrupling of 5-year overall survival with standard platinum doublets, which is approximately 4% for patients with metastatic NSCLC.
That is the good news, but the not-so-good news is that no biomarkers for response or survival were identified.
“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 investigator Julie Brahmer, MD, MSc, Interim Director, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 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 ligand 1 (PD-L1) expression, including patients who were previously treated with 1 to 5 systemic therapies. The study had 3 dosing cohorts, nivolumab 1 mg/kg, 3 mg/kg, and 10 mg/kg given intravenously every 2 weeks for less than 96 weeks. Dr Brahmer presented pooled data for the 3 cohorts at the 2017 American Association for Cancer Research meeting.
The estimated rate of 5-year overall survival was 16%. The median overall survival was 9.9 months, at a minimum of 58 months of follow-up. The 5-year survival rates were consistent for patients with squamous (16%) and nonsquamous (15%) histology.
In 68 of the 129 patients with evaluable PD-L1 expression (53% of patients), the 5-year survival rates increased in a linear fashion with the increasing rates of PD-L1 expression. The 5-year survival rates were 20% in patients with PD-L1 expression <1%; 23% in those with PD-L1 expression ≥1%; and 43% in those with PD-L1 expression ≥50%. PD-L1 status was not evaluable in 47% of the patients. Among patients with unknown PD-L1 expression levels, the estimated 5-year overall survival was 10%.
Of 16 patients who survived for at least 5 years, 9 were male and 12 were current smokers at trial enrollment. Twelve had a partial response, 2 patients had stable disease, and 2 had progressive disease as best response to treatment. Overall, 8 patients completed 2 years of treatment, with no side effects, and 4 stopped early because of side effects. None of these 12 patients required further treatment.
Some Patients Can Stop Nivolumab Therapy After 2 Years
No pattern was observed for clinical and tumor characteristics that could predict survival in this study. Further study is needed to identify patients with NSCLC who may have a good outcome with the use of nivolumab, Dr Brahmer emphasized.
“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 patients with NSCLC do not need indefinite treatment. We are continuing to look for biomarkers. In this trial, no characteristic stands out to identify long-term survivors.”