Ending IO at 2 Years May Be Reasonable for Patients With NSCLC

Lova L. Sun, MD, MSCE

In patients with non–small cell lung cancer (NSCLC) who were progression-free on immunotherapy (IO) at 2 years, 1 in 5 discontinued their treatment. Moreover, there was a lack of overall survival (OS) benefit for these patients, supporting the discontinuation of IO at the 2-year mark.¹

Findings come from a retrospective clinical cohort analysis of 14406 patients with NSCLC receiving IO. According to the investigators led by Lova L. Sun, MD, MSCE, instead of indefinite treatment with IO, it is reasonable to stop treatment at 2 years.

Little is known about the appropriate treatment duration of IO in the NSCLC population. In clinical trials, duration of treatment with IO for patients with NSCLC was capped at 2 years or a maximum of 35 cycles administered every 3 weeks. However, in the clinical practice, most patients are ongoing IO beyond the 2-year mark. Despite studies reporting stable disease after 2 years of IO treatment, there is a reluctance among onco

logists to stop IO.

Lungs in 3D | Image Credit: © yodiyim - www.stock.adobe.com

“As more patients with NSCLC are reaching the 2-year mark of IO, whether to continue or stop treatment is an increasingly common clinical question that providers and patients are grappling with. Since a randomized clinical trial to answer this question will be challenging to conduct and unlikely to yield results for years, we sought to use 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 in the short-term,” Sun, assistant professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania, told Targeted Oncology™.

To investigate the optimal duration of IO in patients with NSCLC, Sun et al utilized a United States (US) oncology database (Flatiron) to assess treatment patterns and survival outcomes correlating with discontinuation of 2-year immune checkpoint inhibitor (ICI) therapy. The difference between long-term ICI use in patients who discontinued treatment at the 2-year mark was compared with those who continued ICI beyond 2 years.

Electronic health records from patients treated at 280 cancer clinics in the US were obtained from the database. The records were of patients aged 18 years or older who were diagnosed with advanced or metastatic NSCLC between 2016 and 2021 who were treated with frontline ICI. Records of patients with EGFR, ALK, or ROS1 alterations were excluded.

The primary analysis was to assess OS, and secondarily, the study looked at the probability of treatment discontinuation in the absence of progression, and outcomes with ICI rechallenge.

Results showed that of the 14406 patients who began frontline IO therapy, 1091were still on treatment at 2 years. At a median follow-up of 14.0 (range, 0.1-50.9), the 2-year OS was 79% (95% CI, 66%-87%) in the fixed-duration cohort vs 81% (95% CI, 77%-85%) in the indefinite-duration group (HR, 1.26; 95% CI, 0.77-2.08).

Although 1 in 5 patients with NSCLC discontinued treatment in the absence of associated progression or death within 2 months, the study showed that rates of ICI discontinuation were not substantially higher at 2 years than at other time points.

Eight patients with NSCLC were rechallenged with ICI monotherapy and 3 were rechallenged with ICI in combination with chemotherapy. The time from cessation of upfront ICI therapy to initiation of second-line therapy was 7.4 (1.8-26.9) months. Moreover, after rechallenge time to second objective progression was 8.1 months.

“This observational study is 1 piece of data that may provide reassurance to providers and patients who wish to stop at 2 years, showing that this strategy does not appear to lead to worse survival compared to continuing immunotherapy. The decision to stop or continue immunotherapy in long-term responders remains an individualized one that requires shared decision making and consideration of each patient’s clinical history, preferences, and risk tolerance,” said Sun.

Sun et al concluded from their research that, “stopping therapy and monitoring rather than continuing immunotherapy indefinitely is a reasonable strategy with sustained clinical benefit.”

_REFERENCE:

_{Sun L, Blieiberg B, Hwang W, et al. Association between duration of immunotherapy and overall survival in advanced non–small cell lung cancer. JAMA Oncol. 2023;9(8):1075-1082. doi:10.1001/jamaoncol.2023.1891}