Overall survival (OS) outcomes did not significantly differ between patients with advanced non-small cell lung cancer (NSCLC) who received immunotherapy indefinitely or for a fixed duration, according to retrospective study results published in JAMA Oncology.

These findings suggest that in the absence of progression, patients in response after 2 years of immunotherapy can safely discontinue treatment and transition to active surveillance. Many clinical trials of immunotherapy in patients with NSCLC set a fixed therapy duration of 2 years, but in clinical practice, treatment often extends beyond this point. Extended exposure to immune checkpoint inhibitors can be associated with increased toxicities and a high financial burden. The optimal duration of immunotherapy remains unconfirmed in the real-world setting.

“Long-term follow-up of large randomized clinical trials has shown that durable responses can be maintained after fixed-duration immune checkpoint inhibitor therapy,” wrote Lova Sun, MD, MSCE, assistant professor of medicine within the Perelman School of Medicine at the University of Pennsylvania, and colleagues. “Despite these encouraging results, there has been substantial hesitation around immune checkpoint inhibitor discontinuation.”

Using electronic health record information in the Flatiron Health database, Sun and colleagues identified patients treated with immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced NSCLC between 2016 and 2021. They stratified patients based on treatment length: fixed-duration (defined as treatment between 700 days and 760 days) and indefinite duration (defined as treatment beyond 760 days). OS beyond 760 days served as the study’s primary outcome measure.

Sun and colleagues identified 14,406 patients who initiated first-line immunotherapy for advanced NSCLC during the study period. Most of these patients discontinued treatment prior to 2 years largely due to death (n = 8,522) or progression/initiation of second-line therapy (n = 2,663). Among the remaining 1,091 patients who continued to receive immunotherapy at 2 years, the fixed-duration group included 113 patients (median age, 69 years; range, 62-75; 54.9% women) and the indefinite duration group included 593 patients (median age, 69 years; range, 62-76; 47.6% women).

A significantly higher percentage of patients in the fixed-duration group received treatment at an academic medical center (22% vs 11%; P = .001) and had a history of smoking (99% vs 93%; P = .01). A numerically higher but non-significant percentage of fixed-duration patients were treated with immune checkpoint inhibitor monotherapy (52% vs 46%).

The median follow-up beginning at day 760 was 14 months (range, 0.1-50.9). The 2-year OS for fixed-duration patients was 79% (95% CI, 66-87), compared to 81% (95% CI, 77-85) for indefinite duration patients. The researchers observed no statistically significant survival differences between fixed-duration and indefinite duration patients in univariate analysis (hazard ratio [HR] for progression or death = 1.26; 95% CI, 0.77-2.08) or multivariable analysis (HR = 1.33; 95% CI, 0.78-2.25).

“Among patients still on immune checkpoint inhibitor treatment at 2 years, only approximately 1 in 5 discontinued treatment in the absence of associated progression or death by the next 2-month time point,” Sun and colleagues wrote. “The discontinuation rates … were not substantially higher at 2 years than at other time points on treatment.”

Eleven patients who received fixed-duration immunotherapy experienced progression after at least 30 days without treatment, of which 10 patients received immunotherapy rechallenge. The median time from discontinuation of frontline immunotherapy to rechallenge was 7.4 months (range, 1.8-26.9), and the median PFS2 for these patients was 8.1 months.

“Given concerns about medical adverse effects and potentially burdensome financial costs associated with the indefinite continuation of immune checkpoint inhibitor therapy, there is a pressing need to answer the question of whether continuing [immunotherapy] beyond 2 years offers clinical benefit compared with stopping treatment,” Sun and colleagues concluded. “These findings provide reassurance that for patients with advanced NSCLC whose disease is still responding to immune checkpoint inhibitor therapy at 2 years, stopping therapy and monitoring rather than continuing immunotherapy indefinitely is a reasonable strategy with sustained clinical benefit.”

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Disclosures: Sun declared financial ties to drugmakers. See full study for details.

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