Based on the preclinical findings, preceding RT enhances efficacy of ICIs. Phase III trial (PACIFIC) evaluating efficacy of durvalumab as consolidation after chemo-RT showed significant improvement in progression-free survival (PFS) in patients with stage III NSCLC (Antonia et al., NEJM 2017). Retrospective analysis showed previous RT resulted longer PFS by ICIs (Shaverdian et al., Lancet Oncol 2017). However, the optimal interval between preceding RT and ICIs has not been clarified.
Between Dec 2015 and Apr 2018, we analyzed consecutive NSCLC patients received ICIs. Patients’ characteristics, driver oncogene alteration (EGFR, ALK and ROS1), RT before ICIs (no RT, definitive or palliative thoracic radiotherapy [TRT] and palliative RT for other sites [other RT]) and PFS were investigated. The interval between the initial day of ICIs and the start date of RT (in patients with RT) or first line chemotherapy (in patients without RT) was classified as follows; within 6 months [<6], 6 to 12 months [6-12] and 12 months or longer [>12].
A total of 294 patients with NSCLC received ICIs; male / female: 186 / 108, median age: 66 (range, 32-85), squamous (Sq) / non-Sq: 60 / 234, driver oncogene alteration (positive / negative or unknown): 47 / 247, regimen (nivolumab / pembrolizumab): 235 / 59, RT (no RT / TRT / other RT): 131 / 83 / 80 and interval time categories (<6 / 6-12 / >12): 91 / 74 / 129. Significantly better PFS of ICIs was demonstrated in patients after TRT (HR 0.71, 95% CI: 0.52-0.97). According to the interval time from preceding RT, efficacy of ICIs was especially enhanced with 6-12 month interval from TRT, even after adjusting by PS, sex, age, histology, tobacco history, ICI regimen and driver oncogene status (adjusted HR 0.37, 95% CI: 0.18-0.76).
Efficacy of ICIs was significantly better in patients after TRT especially between 6 to 12 months from preceding RT.
Clinical trial identification
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H. Horinouchi: Research funding: Ono, MSD, Merck Serono, Novartis, Chugai, Astellas, Daiichi-Sankyo and Genomic Health. Y. Goto: Research funding: MSD, BMS, Chugai. S. Kanda: Consulting or advisory role: AstraZeneca Speaker’s bureau: AstraZeneca, Bristol Myers Squibb, Chugai, Ono Pharmaceutical Research Funding: Abbvie, AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical. Y. Fujiwara: Grants and personal fees: BMS, MSD, AstraZeneca, Grants: Abbvie, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Incyte, Merck Serono, Novartis; Personal fees from Taiho, personal fees outside the submitted work: ONO. N. Yamamoto: Research grants: Quintiles, Astellas, Chugai, Esai, Taiho, BMS, Pfizer, Novartis, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, ONO; Advisory role: Eisai, Takeda, OncoTherapy Science, Otsuka, Boehringer Ingelheim; Honoraria: BMS, Pfizer, AstraZeneca, Eli Lilly, ONO, Chugai. Y. Nakayama: Advisory board: AstraZeneca. Y. Ohe: Research funding: AstraZeneca, Ono Pharmaceutical, Bristol-Myers Squibb, Chugai, MSD, Novartis, Kyorin, Dainippon-Sumitomo, Lilly, Pfizer, Ignyta, Kissei; Honoraria: AstraZeneca, Ono, BMS, Chugai, MSD, Novartis, Daiichi-Sankyo, Boehringer Ingelheim, Bayer, Lilly, Pfizer. All other authors have declared no conflicts of interest.Table: 1498P
PFS of ICIs according to interval from preceding TRT or other RT in comparison with patients without RT
|Total n = 294 HR [95%CI]||Within 6 mo n = 91 HR [95%CI]||6 to 12 mo n = 74 HR [95%CI]||12 mo or longer n = 129 HR [95%CI]|
|TRT||0.71 [0.52-0.97]||0.98 [0.49-1.98]||0.35 [0.17-0.71]||0.92 [0.59-1.43]|
|Other RT||1.02 [0.75-1.39]||0.96 [0.56-1.66]||1.22 [0.66-2.27]||0.89 [0.53-1.48]|