Certain NSCLC Patients May Be Able to Stop Immunotherapy at 2 Years

CHICAGO — Patients with advanced non-small cell lung cancer (NSCLC) who are progression-free may discontinue treatment with frontline immunotherapy after 2 years without compromising overall survival (OS), a retrospective cohort study suggested.

While most patients (80%) who reached that 2-year landmark continued to receive rather than discontinue therapy, there was no statistically significant difference in OS between patients who discontinued treatment (fixed-duration) and those who continued indefinitely, reported Charu Aggarwal, MD, MPH, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, during the American Society of Clinical Oncology annual meeting.

When comparing survival beyond 760 days, the 2-year OS rate was 79% in the fixed-duration group and 81% in the indefinite-duration group. There was no statistically significant difference in OS between the groups either on univariate (HR 1.26, 95% CI 0.77-2.08, P=0.36) or multivariable (HR 1.33, 95% CI 0.78-2.25, P=0.29) Cox regression, the study authors noted in JAMA Oncology.

“I hope our study presents to physicians and patients that now there is real-world evidence that suggests that you can stop immunotherapy without significant consequences, and provides the clinical guidance and comfort level needed to change practice,” Aggarwal told MedPage Today.

The researchers also identified a subset of 11 patients in the fixed-duration cohort who subsequently had progression and were rechallenged with either immune checkpoint inhibitor (ICI) monotherapy or ICI in combination with chemotherapy. 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.

“So we showed in a small subset of patients that once you stop immunotherapy, and physicians choose to rechallenge with immunotherapy, you can actually get a response,” Aggarwal said.

Two Years — or More?

While the management of patients with advanced NSCLC has changed with the introduction of ICIs, the optimal duration of these therapies is unknown. Aggarwal and colleagues pointed out that patients in key pivotal studies reporting on the use of first-line immunotherapy were treated with ICI therapy for up to 2 years, but that in clinical practice patients often continue therapy beyond that point.

“This is based on different factors, including patient preference — why rock the boat if you have a good thing going?” Aggarwal said. “But, there is really a lack of evidence demonstrating whether continued immunotherapy is better or worse.”

She also noted that there are toxicity concerns with continued immunotherapy, including the costs associated with continued therapy, and the potential for immune-related toxicity.

“And there is time toxicity,” she added. “Patients still have to come every 3 or 6 weeks, depending on the schedule of immunotherapy.”

In an editor’s note accompanying the study, Howard (Jack) West, MD, of the City of Hope Comprehensive Cancer Center in Duarte, California, observed that while there are limitations to retrospective data, a prospective randomized clinical trial would be difficult to conduct and take years to complete.

“In the meantime, the perfect should not be the enemy of the good,” he wrote, adding that the data from this study “may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same OS as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our healthcare system.”

For this study, Aggarwal and colleagues used the Flatiron Health database to identify 14,406 adults with a new diagnosis of advanced or metastatic NSCLC between 2016 and 2021, who received frontline ICI therapy (alone or in combination with chemotherapy).

Of these patients, 13,315 who discontinued therapy before 700 days were excluded, with the majority either having died or initiated second-line therapy with 2 years of treatment. Among the remaining 1,039 patients, 113 patients (median age 69 years, 54.9% female, 76.1% white) were included in the fixed-duration group, and 593 patients (median age 69 years, 47.6% female, 69.8% white) were included in the indefinite-duration group.

Patients in the fixed-duration group were more likely to have a history of smoking (99% vs 93%, P=0.01) and be treated at an academic center (22% vs 11%, P=0.001).

The authors noted that residual confounding was possible, as unmeasured factors may influence the decision to continue or discontinue treatment at 2 years.