Background The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of non-small cell lung cancer (NSCLC). Radiotherapy (RT) has shown potential to enhance immune responses by modulating the tumor immune microenvironment, but few data are available. The optimal timing of RT in combination with ICIs and its effect on survival has not yet been established. Methods This retrospective analysis included 350 patients with stage IV NSCLC who received from 2019 to 2024, first-line ICI ± chemotherapy (ChT), according to tissue PD-L1 status (tPD-L1). Among these, 136 patients received RT within 3 months before (pre-ICIs) or after (post-ICIs) the initiation of ICIs. Baseline clinical characteristics were compared between the pre-ICIs and post-ICIs groups. RT sites included bone, brain, and thoracic regions. According to tPD-L1 status, 85 patients (62%) received ICI in combination with ChT, while 51 (38%) as ICI monotherapy alone. Overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate models. Results Among patients under RT, 81 were in the pre-ICIs group and 55 in the post-ICIs group. Clinical characteristics were similar between the groups, except for ECOG PS (Eastern Cooperative Oncology Group Performance Status). The post-ICIs group showed significantly longer OS (HR: 0.28; 95% CI: 0.18–0.44; p<0.0001) and PFS (HR: 0.34; 95% CI: 0.23–0.51; p<0.0001) compared to the pre-ICIs group. In multivariate analysis, the HR for OS was 0.30 (95% CI: 0.19–0.47, p<0.0001) and for PFS was 0.36 (95% CI: 0.23–0.54, p<0.0001), adjusting for PS, number of metastasis sites, tPD-L1, RT site, and first-line regimen (ICIs±ChT). Conclusions Our study suggest that RT administered during first-line ICIs therapy, rather than prior to ICIs initiation, leads to improved survival outcomes in metastatic NSCLC patients. These results were consistent across different clinical characteristics and treatment regimens.
1901P Impact of radiotherapy timing on immune checkpoint inhibitors efficacy in metastatic non-small cell lung cancer / Siringo, M.; Gentile, G.; Sabatini, A.; Larocca, F.; Spagnuolo, A.; Tramontano, E.; Magri, V.; Bulzonetti, N.; Gelibter, A. J.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 36:(2025). (Intervento presentato al convegno esmo 2025 tenutosi a berlino) [10.1016/j.annonc.2025.08.2525].
1901P Impact of radiotherapy timing on immune checkpoint inhibitors efficacy in metastatic non-small cell lung cancer
Siringo, M.
Primo
;Gentile, G.Secondo
;Sabatini, A.;Larocca, F.;Spagnuolo, A.;Tramontano, E.;Magri, V.;Gelibter, A. J.Ultimo
2025
Abstract
Background The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of non-small cell lung cancer (NSCLC). Radiotherapy (RT) has shown potential to enhance immune responses by modulating the tumor immune microenvironment, but few data are available. The optimal timing of RT in combination with ICIs and its effect on survival has not yet been established. Methods This retrospective analysis included 350 patients with stage IV NSCLC who received from 2019 to 2024, first-line ICI ± chemotherapy (ChT), according to tissue PD-L1 status (tPD-L1). Among these, 136 patients received RT within 3 months before (pre-ICIs) or after (post-ICIs) the initiation of ICIs. Baseline clinical characteristics were compared between the pre-ICIs and post-ICIs groups. RT sites included bone, brain, and thoracic regions. According to tPD-L1 status, 85 patients (62%) received ICI in combination with ChT, while 51 (38%) as ICI monotherapy alone. Overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate models. Results Among patients under RT, 81 were in the pre-ICIs group and 55 in the post-ICIs group. Clinical characteristics were similar between the groups, except for ECOG PS (Eastern Cooperative Oncology Group Performance Status). The post-ICIs group showed significantly longer OS (HR: 0.28; 95% CI: 0.18–0.44; p<0.0001) and PFS (HR: 0.34; 95% CI: 0.23–0.51; p<0.0001) compared to the pre-ICIs group. In multivariate analysis, the HR for OS was 0.30 (95% CI: 0.19–0.47, p<0.0001) and for PFS was 0.36 (95% CI: 0.23–0.54, p<0.0001), adjusting for PS, number of metastasis sites, tPD-L1, RT site, and first-line regimen (ICIs±ChT). Conclusions Our study suggest that RT administered during first-line ICIs therapy, rather than prior to ICIs initiation, leads to improved survival outcomes in metastatic NSCLC patients. These results were consistent across different clinical characteristics and treatment regimens.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
