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. 2025 Jan 8;6(3):100790.
doi: 10.1016/j.jtocrr.2025.100790. eCollection 2025 Mar.

Impact of Immune Checkpoint Inhibitors and Local Radical Treatment on Survival Outcomes in Synchronous Oligometastatic NSCLC

Mandy Jongbloed  1 , Valentina Bartolomeo  2   3   4 , Martina Bortolot  5 , Shahan Darwesh  1 , Jarno W J Huijs  1 , Safiye Dursun  1 , Juliette Degens  6 , Ben E E M van den Borne  7 , Maggy Youssef-El Soud  8 , Marcel Westenend  9 , Cordula Pitz  10 , Dirk K M De Ruysscher  4 , Lizza E L Hendriks  1
Affiliations

Impact of Immune Checkpoint Inhibitors and Local Radical Treatment on Survival Outcomes in Synchronous Oligometastatic NSCLC

Mandy Jongbloed et al. JTO Clin Res Rep. .

Abstract

Introduction: The impact of an immune checkpoint inhibitor (ICI)-based systemic treatment strategy with or without local radical treatment (LRT) on outcomes for patients with NSCLC and synchronous oligometastatic disease (sOMD) is unknown.

Methods: Multicenter retrospective study including adequately staged patients, with sOMD NSCLC (maximum five metastases in three organs [European Organization for Research and Treatment of Cancer definition]) between January 1, 2015 and December 31, 2022, treated with a first-line ICI-based versus chemotherapy-only regimen. Primary end points were progression-free survival and overall survival (OS) for an ICI-based versus chemotherapy-only strategy. Subgroup analyses were performed for patients who were deemed candidates for LRT in the multidisciplinary meeting and those proceeding to LRT.

Results: A total of 416 patients were included, treated with chemotherapy-ICI (n = 138) or chemotherapy-only (n = 278), 319 out of 416 were deemed candidates by multidisciplinary meetings for LRT, whereas 192 (60%) proceeded to LRT. The median OS was significantly longer in the chemotherapy-ICI compared with the chemotherapy-only group (33.6 versus 15.9 mo, hazard ratio [HR] = 0.5, 95% confidence interval [CI]: 0.4-0.7, p < 0.001), in the subgroups who were candidate for LRT (36.1 versus 17.2 mo, HR = 0.5, 95% CI: 0.4-0.7, p < 0.001) and those proceeding to LRT (not reached versus 23.1 mo, HR = 0.4, 95% CI: 0.2-0.7, p < 0.001). In multivariate analysis, an ICI-based strategy was associated with improved survival in the total group (HR = 0.6, 95% CI: 0.4-0.9, p < 0.001), in those with intention of LRT (HR = 0.6, 95% CI: 0.4-0.9, p = 0.02) and those who proceeded to LRT (HR = 0.3, 95% CI: 0.1-0.6, p = 0.002).

Conclusions: An ICI-based systemic treatment strategy (±LRT) is associated with improved survival compared with chemotherapy-only (±LRT) for patients with sOMD NSCLC. Prospective randomized trial data are necessary to identify patients most likely to benefit from adding LRT.

Keywords: Immune checkpoint inhibitors; NSCLC; Overall survival; Progression free survival; Synchronous oligometastatic disease.

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Conflict of interest statement

Dr. Hendriks: outside of this manuscript personal fees as an invited speaker from AstraZeneca, Bayer, Eli Lilly, Merck Sharp & Dohme, high5oncology, Takeda, Janssen, GlaxoSmithKline, Sanofi, Pfizer (Inst), Medtalks, Benecke, VJOncology, Medimix (self).; all payments were paid to the institution with the exception of Medtalks, Benecke, VJOncology, Medimix; fees paid to her institution for advisory board membership from Advisory boards: Amgen, Boehringer Ingelheim, Eli Lilly, Novartis, Pfizer, Takeda, Merck, Janssen, Merck Sharp & Dohme, Anheart, Bayer, AZ, Pierre Fabre, Bristol-Myers Squibb, AbbVie, Daiichi; institutional research grants from 10.13039/100004337Roche 10.13039/100004328Genentech, 10.13039/100004325AstraZeneca, Boehringer Ingelheim, Takeda, Merck, Pfizer, Novartis, and Gilead; institutional funding as a local principal investigator from AstraZeneca, GlaxoSmithKline, Novartis, Merck, Roche, Takeda, Blueprint, Mirati, AbbVie, Gilead, Merck Sharp & Dohme, Merck, Amgen, Boehringer Ingelheim, Pfizer; Member guideline committees: Dutch guidelines on NSCLC, brain metastases and leptomeningeal metastases (self), ESMO guidelines on metastatic NSCLC and SCLC (nonfinancial) Other (nonfinancial): secretary NVALT studies foundation, subchair European Organization for Research and Treatment of Cancer metastatic NSCLC systemic therapy, vice-chair scientific committee Dutch Thoracic Group. Dr. de Ruysscher: outside of this manuscript research grant/support/Advisory Board: Institutional financial interests (no personal financial interests) from AstraZeneca, Bristol-Myers Squibb, BeiGene, Philips, Olink and Advisory Board: Institutional financial interests (no personal financial interests) for Eli Lilly. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of patient inclusion and selection with synchronous oligometastatic NSCLC. TKI, tyrosine kinase inhibitor; RT, radiotherapy; MDT, multidisciplinary team; ICI, immune checkpoint inhibitor; LRT, local radical treatment.
Figure 2
Figure 2
(A) Progression-free survival in the total group, split for (chemo)-ICI versus chemo-only treatment. (B) Overall survival in the total group, split for (chemo)-ICI versus chemo-only treatment. (C) Progression-free survival in the subgroup of patients with the intention of local radical therapy, split for (chemo)-ICI versus chemo-only treatment. (D) Overall survival in the subgroup of patients with the intention of local radical therapy, split for (chemo)-ICI versus chemo-only treatment. (E) Progression-free survival in the subgroup of patients actually receiving local radical therapy, split for (chemo)-ICI versus chemo-only treatment. (F) Overall survival in the subgroup of patients actually receiving local radical therapy, split for (chemo)-ICI versus chemo-only treatment. chemo, chemotherapy; CI, confidence interval; HR, hazard ratio; ICI, immune checkpoint inhibitor.
See this image and copyright information in PMC

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