Progression-free on immunotherapy for NSCLC? Stopping treatment at 2 years may be OK

For patients with advanced nonsmall cell lung cancer (NSCLC) who remain progression-free on immune checkpoint inhibitor (ICI)-based therapy at 2 years, continuing treatment does not appear to confer any survival advantage as opposed to stopping, according to a retrospective study presented at ASCO 2023.

In a cohort of 706 patients who reached 2 years of ICI in the frontline setting, about one in five discontinued treatment in the absence of progression or death, reported lead study author Dr Lova Sun from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, US.

Overall survival among patients who stopped ICI at 2 years (between 700 and 760 days; fixed-duration group, n=113) did not differ from that among patients who continued treatment beyond 2 years (>760 days; indefinite-duration group, n=593) both in univariate (hazard ratio [HR], 1.26, 95 percent confidence interval [CI], 0.77–2.08; p=0.36) or multivariable (HR, 1.33, 95 percent CI, 0.78–2.25; p=0.29) Cox regression analyses. [ASCO 2023, abstract 9101]

The 2-year overall survival from 760 days was 79 percent (95 percent CI, 66–87) in the fixed-duration group and 81 percent (95 percent CI, 77–85) in the indefinite-duration group.

“In line with previous studies that have shown durable benefit after stopping ICI at 2 years, the present study supports treatment discontinuation at 2 years as a valid approach that does not appear to compromise survival outcomes,” Sun pointed out. [J Clin Oncol 2021;39:2339-2349; J Clin Oncol 2020;38:1580-1590]

Of note, the baseline characteristics in the fixed-duration (median age 69 years, 54.9 percent women, 76.1 percent White) and indefinite-duration groups (median age 69 years, 47.6 percent women, 69.8 percent White) were well balanced. The only exception, according to Sun, was that patients in the fixed-duration group were more likely to be treated at an academic centre (22 percent vs 11 percent; p=0.001) and have a history of smoking (99 percent vs 93 percent; p=0.01).

“[The said] differences may reflect providers’ comfort level in discontinuing ICI therapy for a subgroup of patients known to respond well to immunotherapy (squamous histologic type, smoking history). These findings augment the literature by demonstrating that even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” she said.

ICI rechallenge

Even if progression occurs after ICI cessation, Sun stressed that rechallenge with ICI may yield favourable outcomes.

Among 11 patients in the fixed-duration group who subsequently had progression and underwent rechallenge therapy, median progression-free survival after rechallenge was 8.1 months, with more than one-third of patients still on treatment at the data cutoff point. The median time from cessation of frontline ICI to initiation of rechallenge therapy was 7.4 months.

“Results from this small cohort in a clinical setting align with the promising results seen with ICI rechallenge in long-term follow-up of randomized clinical trials,” according to Sun.

Taken together, the present data provide reassurance “that for patients with advanced NSCLC whose disease is still responding to ICI therapy at 2 years, stopping therapy and monitoring rather than continuing immunotherapy indefinitely is a reasonable strategy with sustained clinical benefit,” she concluded.

Practice guidance

In an online editorial, Dr Howard West, of the City of Hope Comprehensive Cancer Center, Duarte, California, US, and who was involved in the study, echoed Sun.

West wrote that while Sun and colleague’s retrospective clinical data have clear limitations, the study instils confidence in both clinicians and patients that discontinuing ICI at 2 years can confer the same overall survival as extended treatment, with the added advantage of “lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for the healthcare system.” [JAMA Oncol  2023;doi:10.1001/jamaoncol.2023.1811]

“We may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available. In the meantime, the perfect should not be the enemy of the good,” he said.