Association Between Duration of Immunotherapy and Overall Survival in Advanced Non–Small Cell Lung Cancer

Abstract

ImportanceFor patients with advanced non–small cell lung cancer (NSCLC) treated with frontline immunotherapy-based treatment, the optimal duration of immune checkpoint inhibitor (ICI) treatment is unknown.ObjectiveTo assess practice patterns surrounding ICI treatment discontinuation at 2 years and to evaluate the association of duration of therapy with overall survival in patients who received fixed-duration ICI therapy for 2 years vs those who continued therapy beyond 2 years.Design, Setting, and ParticipantsThis retrospective, population-based cohort study included adult patients in a clinical database diagnosed with advanced NSCLC from 2016 to 2020, who received frontline immunotherapy-based treatment. The data cutoff was August 31, 2022; data analysis was conducted from October 2022 to January 2023.ExposuresTreatment discontinuation at 2 years (between 700 and 760 days, fixed duration) vs continued treatment beyond 2 years (greater than 760 days, indefinite duration).Main Outcomes and MeasuresOverall survival from 760 days was analyzed using Kaplan-Meier methods. Multivariable Cox regression that adjusted for patient-specific and cancer-specific factors was used to compare survival beyond 760 days between the fixed-duration group and the indefinite-duration group.ResultsOf 1091 patients in the analytic cohort who were still on ICI treatment at 2 years after exclusion criteria for death and progression were applied, 113 patients (median [IQR] age, 69 [62-75] years; 62 [54.9%] female; 86 [76.1%] White) were in the fixed-duration group, and 593 patients (median [IQR] age, 69 [62-76] years; 282 [47.6%] female; 414 [69.8%] White) were in the indefinite-duration group. Patients in the fixed-duration group were more likely to have a history of smoking (99% vs 93%; P = .01) and be treated at an academic center (22% vs 11%; P = .001). Two-year overall survival from 760 days was 79% (95% CI, 66%-87%) in the fixed-duration group and 81% (95% CI, 77%-85%) in the indefinite-duration group. There was no statistically significant difference in overall survival between patients in the fixed-duration and indefinite-duration groups, either on univariate (hazard ratio [HR] 1.26; 95% CI, 0.77-2.08; P = .36) or multivariable (HR 1.33; 95% CI, 0.78-2.25; P = .29) Cox regression. Approximately 1 in 5 patients discontinued immunotherapy at 2 years in the absence of progression.Conclusions and RelevanceIn a retrospective clinical cohort of patients with advanced NSCLC who were treated with immunotherapy and were progression-free at 2 years, approximately only 1 in 5 discontinued treatment. The lack of statistically significant overall survival advantage for the indefinite-duration cohort on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years.

Clinical outcomes of atezolizumab versus standard-of-care docetaxel with and without ramucirumab in patients with advanced non-small-cell lung cancer who received prior immunotherapy

“…In addition, we also observed significantly improved OS (17.7 vs. 7.7 vs. 8.9 months) in the Atezo group in compared to other two groups despite small sample size. This discordance between PFS and OS is consistent with previous studies that showed atezolizumab and other ICIs may have delayed anti-tumor effect that lasts beyond treatment period ( 6 , 14 , 15 ). Median PFS correlates poorly with median OS and may underestimate the clinical benefits of immunotherapy ( 16 , 17 ).…”

Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal ctDNA and Immune Cell Compartment Tracking in Lung Cancer

“…Similarly, treatment de-escalation in patients who attain a molecular response indicated by ctDNA clearance may reduce the personal and financial burden of overtreatment. Elective immunotherapy discontinuation past 2 years is well supported ( 44–46 ) and proof-of-concept studies have shown that sustained ctDNA clearance may identify candidates for immunotherapy de-escalation ( 47 ); nevertheless, there are currently no molecularly informed approaches to guide treatment de-escalation. Translating these findings to the clinic, early on-therapy ctDNA persistence prior to and independent of the radiographic response can identify patients not attaining therapeutic benefit, who can be rapidly and accurately guided to alternate therapies.…”

Changes in Global Quality of Life after treatment with immune checkpoint inhibitors in patients with advanced stage lung cancer in the Netherlands – a 2015-2021 cohort study

“…Very few methodical studies have been published on post-treatment longer-term QoL from observational real-world data focusing on immunotherapy as well as on other cancer treatments such as chemotherapy and radiotherapy 11–13 16 . Moreover, studies that investigated QoL in this population so far had a follow-up of under one year 17 , while ICI treatment regimens typically have an intended duration of two years 18 . Patients’ QoL may therefore be affected, even long after treatment with ICIs is initiated.…”