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Comment
. 2023 Aug 1;9(8):1075-1082.
doi: 10.1001/jamaoncol.2023.1891.

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

Lova Sun  1 , Benjamin Bleiberg  1 , Wei-Ting Hwang  2 , Melina E Marmarelis  1 , Corey J Langer  1 , Aditi Singh  1 , Roger B Cohen  1 , Ronac Mamtani  1 , Charu Aggarwal  1
Affiliations
Comment

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

Lova Sun et al. JAMA Oncol. .

Abstract

Importance: For 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.

Objective: To 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 participants: This 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.

Exposures: Treatment 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 measures: Overall 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.

Results: Of 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 relevance: In 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Sun reported consulting with Regeneron, GenMab, Seagen, and Bayer; and funding to institution from Blueprint Research, Seagen Research, and IO Biotech Research outside the submitted work. Dr Marmarelis reported research funding to institution from Eli Lilly, AstraZeneca, Merck, and Genentech; consulting with AstraZeneca, Novocure, Boehringer Ingelheim, Janssen, Takeda, Blueprint Pharmaceuticals, Bristol Myers Squibb, and Ikena; honorarium from Thermo Fisher; and stock in Gilead Sciences, Portola Pharmaceuticals, Merck, Bluebird Bio, Johnson & Johnson, and Pfizer. Dr Langer reported grants from Merck, AstraZeneca, and Genentech/Roche; personal fees from Gilead and Pfizer outside the submitted work; and stocks in VALOR and RTOG Foundation. Dr Singh reported research funding to institution from Jazz Pharmaceuticals. Dr Mamtani reported grants from Merck and Astellas; and personal fees from Seagen and Flatiron outside the submitted work. Dr Aggarwal reported consulting for Genentech, Lilly, Celgene, Merck, AstraZeneca, Blueprint, Shionogi, Turning Point, Daiichi, Sanofi/Regeneron, Eisai, Beigene, Pfizer, Janssen, and Boehringer Ingelheim outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram
Abbreviations: NSCLC, non–small cell lung cancer; ICI, immune checkpoint inhibitor. aExclusion criterion applied to enable landmark Kaplan-Meier analysis starting at 760 days. bPatients in the fixed-duration group were excluded if death occurred in the same month as, or the month after, their end of treatment, as these patients’ treatment cessation was more likely related to death than the decision to pursue fixed-duration therapy.
Figure 2.
Figure 2.. Overall Survival
Kaplan-Meier curve of overall survival from 2 years (760 days) from immune checkpoint inhibitor (ICI) treatment initiation in the fixed-duration cohort (stopped treatment at 2 years; 700-759 days of treatment) and indefinite-duration cohort (at least 760 days of treatment).
Figure 3.
Figure 3.. Treatment Discontinuation Over Time and ICI Rechallenge
A, The cumulative incidence of treatment discontinuation in the absence of progression or death over time (in months) from treatment initiation. Patients with progression within 60 days of discontinuation or death within 6 months of discontinuation were classified as having a competing event for this analysis. B, Swimmer plot with fixed-duration treatment group patients rechallenged with ICI-based therapy. Abbreviations: ICI, immune checkpoint inhibitor; PD, progressive disease.
See this image and copyright information in PMC

Comment on

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