Overall Survival in Advanced NSCLC Unaffected by Immunotherapy Duration Beyond 2 Years

According to a study published in JAMA Oncology, patients with non–small cell lung cancer (NSCLC) can feel reassured that discontinuing immunotherapy after 2 years will not negatively affect their prognosis.

The administration of immune checkpoint inhibitors (ICIs) has dramatically altered the treatment of patients with advanced or metastatic NSCLC; however, there is not a consensus on the optimal duration of ICI treatment.

The authors point to previous studies detailing the potential dangers that accompany indefinite-duration immunotherapy, which include increased risks of adverse effects and financial burden. Associations between the duration of ICI and clinical outcomes could have meaningful impacts on the clinical management of advanced or metastatic NSCLC.

Researchers analyzed data from the Flatiron Health database, an electronic health record holding information from 280 cancer clinics throughout the United States. They separated patients into 2 cohorts: a fixed-duration group of patients whose ICI-based therapy continued for 700 to 759 days (approximately 2 years after the initiation of therapy) and an indefinite-duration group of patients who continued ICI-based therapy beyond 760 days.

Eligible patients were aged at least 18 years and had newly diagnosed advanced or metastatic NSCLC. Patients were excluded if they discontinued their treatment before the 700-day minimum, had any documented disease progression between the start of ICI and 760 days, died over the course of treatment, or were lost to follow-up before 760 days.

A total of 113 patients were included in the fixed-duration group and 593 were included in the indefinite-duration group. After the 760-day mark following the start of ICI, there was a median follow-up time of 14 months.

Overall survival was measured 2 years after the 760-day mark (4 years after the initiation of treatment). The fixed-duration group survival rate was 79% whereas the indefinite-duration group rate was 81%. The findings did not reveal any statistically significant difference between survival in the 2 groups in either univariate (HR, 1.26, 95% CI, 0.77-2.08; P = .36) or multivariable (HR, 1.33; 95% CI, 0.78-2.25; P = .29) analyses. This was despite the finding that the fixed-duration group patients were more likely to have a history of smoking, receive treatment at an academic center, and have squamous cell carcinoma and ICI monotherapy.

Among the limitations identified by the authors was the possibility of unmeasurable factors that may have influenced patients’ decisions to halt or continue treatment at or beyond 2 years. Authors also noted that patients who stopped treatment at 2 years because of disease progression that happened just after the 760-day mark could have been mislabeled and assigned to the fixed-duration group. This study investigated only a 2-year frame for immunotherapy duration, which, as they mentioned, leaves out data from other time points that could further help elucidate their underlying question of how much immunotherapy is enough.

Overall, the findings are valuable for informing the approach of both patients and doctors in the management of NSCLC. The results of this study demonstrate that the cessation of immunotherapy at 2 years does not appear to worsen survival outcomes in patients with NSCLC. Researchers concluded by reemphasizing that “stopping therapy and monitoring rather than continuing immunotherapy indefinitely is a reasonable strategy with sustained clinical benefit.”

Reference

Sun L, Bleiberg B, Hwang WT, et al. Association between duration of immunotherapy and overall survival in advanced non–small cell lung cancer. JAMA Oncol. Published online June 4, 2023. doi:10.1001/jamaoncol.2023.1891