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Lung cancer is the second most common cancer in the U.S. and the leading cause of cancer-related mortality.¹ The past decade has seen dramatic progress in the management of non-small cell lung cancer (NSCLC), with major advances in screening, diagnosis, and treatment. Improvements in systemic treatment have been driven by the development of molecularly targeted agents, including immune checkpoint inhibitors (ICI), which have become standard of care as first-line treatment for advanced NSCLC.^2,3 

While many clinical trials have used either a maximum 2-year fixed duration of ICI treatment or continuous treatment until documented disease progression, the optimal duration of ICI treatment for patients with advanced NSCLC remains unknown.⁴

鈥淎s more patients with NSCLC are reaching the 2-year mark of immunotherapy, whether to continue or stop treatment is an increasingly common clinical question that providers and patients are grappling with,鈥� says Lova Sun, MD, MSCE, an assistant professor of medicine (hematology/oncology) at the Hospital of the University of Pennsylvania, in Philadelphia. 

Two years or longer? Searching for answers

To gain clarity around the significance of the 2-year mark for ICI treatment among those with NSCLC, Dr. Sun and her colleagues conducted a retrospective cohort study to compare survival outcomes among patients who stopped ICI-containing treatment at 2 years to those who continued treatment beyond 2 years.⁵

鈥淪ince a randomized clinical trial to answer this question would be challenging to conduct and unlikely to yield results for years, we used a large, observational, nationwide database to investigate the question of whether continuing immunotherapy beyond 2 years is associated with better survival, in order to help guide these decisions,鈥� says Dr. Sun, who is the lead author of the study. 

The research team used data from electronic health records to identify persons diagnosed with advanced NSCLC from 2016 to 2020 who initiated first-line treatment with an ICI, either alone or in combination with chemotherapy (n=14,406). Of these, the vast majority (n=13,315) discontinued treatment before 2 years, either because they died (n=8522) or because they initiated second-line treatment, had disease progression, or both (n=2663). After applying exclusion criteria (death or disease progression) to those still on their initial treatment at 2 years (n=1091), the investigators compared the outcomes of 113 patients in the fixed-duration therapy group and 593 in the indefinite-duration therapy group.

What the investigators discovered

The study found that, among those in the fixed-duration group, 2-year overall survival (OS) was 79% (95% confidence interval [CI] 66% to 87%), compared to 81% (95% CI 77% to 85%) in the indefinite-duration group.⁵ Using Cox regression models, Dr. Sun and her colleagues found no significant difference in OS between those who received fixed-duration of therapy and those in the indefinite-duration group, either on univariate analysis (hazard ratio [HR] 1.26, 95% CI 0.77 to 2.08; P=.36) or multivariable analysis (HR 1.33, 95% CI 0.78 to 2.25; P=.29). Approximately 1 in 5 patients discontinued ICI-based treatment at 2 years in the absence of progression.

鈥淭he low rate of treatment discontinuation at 2 years was perhaps the most surprising finding of our study,鈥� Dr. Sun says. 鈥淭his reflects significant provider and patient hesitation to stop treatment and indicates that the majority of patients nationwide are being continued on checkpoint inhibitor therapy beyond 2 years.鈥� 

Identifying the main take-aways

The authors noted 3 key clinical implications of their study. 鈥淥ur findings provide reassurance that, for patients and providers who are considering stopping at 2 years, this strategy does not appear to compromise outcomes,鈥� Dr. Sun says. Second, the study demonstrated that patients who underwent fixed-duration treatment benefited from ICI rechallenge even after disease progression, with a median progression-free survival of 8.1 months. Finally, some 80% of those in this analysis who survived or had no disease progression continued ICI-based treatment after 2 years. 

In an accompanying editorial, medical oncologist Howard (Jack) West, MD, City of Hope Comprehensive Cancer Center, Duarte, Calif., agreed that a prospective randomized clinical trial to confirm the optimal duration of ICI treatment for those with advanced NSCLC would be difficult to complete and the 鈥渞esults will take many years to become available.鈥�⁶ In the meantime, he says, the current analysis offers assurance that limiting treatment to 2 years confers the same survival benefit as extended treatment, with less drug exposure for patients and lower costs to the healthcare system.

Published: October 12, 2023