Differential therapeutic benefit of platinum-doublet chemotherapies with ICIs based on the classification by combined with smoking status and PD-L1 expression in patients with advanced NSCLC.

person Akito Fukuda National Cancer Center Hospital, Chuo-KU, Japan info_outline Akito Fukuda, Tatsuya Yoshida, Ken Masuda, Yuki Shinno, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Yuichiro Ohe

Authors person Akito Fukuda National Cancer Center Hospital, Chuo-KU, Japan info_outline Akito Fukuda, Tatsuya Yoshida, Ken Masuda, Yuki Shinno, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Yuichiro Ohe Organizations National Cancer Center Hospital, Chuo-KU, Japan, National Cancer Center Hospital, Tokyo, Japan, Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan Abstract Disclosures Research Funding No funding received Background: Chemotherapy combined with immune checkpoint inhibitors (Chemo-ICIs) has been the standard of care for advanced NSCLC patients. Smoking status is associated with PD-L1 expression and the TILs within tumor microenvironment, which leads to the efficacy of ICIs. It remains unclear how the combined with PD-L1 expression and smoking status affect the efficacy of Chemo-ICIs. Methods: We retrospectively reviewed advanced NSCLC patients without driver mutation (EGFR, ALK, ROS-1, BRAF) who received Chemo-ICIs from January 2019 to June 2021, and Chemo from January 2014 to December 2016 as a first-line therapy at the National Cancer Center Hospital, Tokyo, Japan. The additional benefit of ICIs to chemotherapy were evaluated by comparing the Chemo-ICIs group with Chemo group. Results: During study period, 225 patients received Chemo-ICIs and 133 received Chemo as a first line therapy. Overall response rate (ORR) and progression free survival (PFS) was significantly better in the Chemo-ICIs group than the Chemo group (ORR: 44.9% vs. 40.2%, p=0.01, and median PFS: 8.2 months vs. 6.2 months, P<0.001). The median overall survival was 27.9 months in Chemo-ICIs and 20.4 months in chemo (P=0.14). In the subgroup analysis of PFS, the benefit of Chemo-ICIs compared to Chemo was not observed in never-smoker patients (8.9months vs 8.8months, P=0.27). In contrast, among smoker patients, Chemo-ICIs showed significant longer PFS compared to Chemo (7.5 months vs 5.7 months, P<0.001). Next, patients received Chemo-ICIs were classified into six groups, based on the smoking status (never smoker or smoker) and PD-L1 expression (TPS: 0%, 1-49%, or 50%). Chemo-ICIs showed better PFS rate at 12 months in the smoker/ TPS ≥50% group (42.2% vs 25.0%, p=0.03), and the never smoker/TPS ≥50% group (75.0% vs 27.3%, p=0.05) compared with Chemo (Table). In patients with 1-49% TPS, compared to the Chemo group, significant PFS benefit of ICIs was observed only in smoker patients (42.2% vs 25.0%, p=0.003), not in never smoker patients (46.2% vs 27.3%, p=0.13). In patients with 0% TPS, although the additional benefit of ICIs to Chemo was not observed both in never and smoker patients, PFS rate at 12 months in never smoker (13.3%) was lowest among all six groups. Conclusions: Our study suggested that additional benefit of ICIs to chemotherapy could be predicted by combined with smoking status and PD-L1 expression. PFS rate at 12 months. Smoking status TPS PFS ratio at 12 months, (95% CI) P value Chemo-ICIs Chemo Never smoker 0% 13.3% (2.0-35.0) 27.3% (12.1-44.9) 0.47 1-49% 46.2% (14.5-73.4) 0.14 ≥50% 75.0% (31.5-93.1) 0.05 Smoker (Past/Current) 0% 26.6% (16.5-37.9) 25.0% (17.0-34.0) 0.13 1-49% 42.2% (29.4-54.6) 0.003 ≥50% 42.4% (28.1-56.0) <0.001 TPS; tumor proportion score, PFS; progression free survival, CI; confidence interval, ICI; immunotherapy.