National Cancer Center Hospital, Tokyo, Japan
Hidekazu Hirano , Yasuhide Yamada , Kengo Nagashima , Nobuyoshi Hiraoka , Shigeki Sekine , Naoki Takahashi , Mizutomo Azuma , Satoru Iwasa , Keisuke Kanato , Nozomu Machida , Takahiro Kinoshita , Hiroaki Hata , Hisato Kawakami , Daisuke Takahari , Toshiyasu Ojima , Shigenori Kadowaki , Narikazu Boku , Yukinori Kurokawa , Masanori Terashima , Takaki Yoshikawa
Background: Although high PD-L1 expression predicts a favorable response of advanced solid tumors to immune checkpoint inhibitors (ICIs), its impact on survival in patients with unresectable/recurrent gastric cancer (GC) has remained unclear. We investigated the prognostic value of PD-L1 expression for survival in unresectable/recurrent GC patients receiving first-line chemotherapy without ICIs. Methods: JCOG1013, a phase 3 randomized trial, demonstrated the addition of docetaxel to cisplatin and S-1 as first-line chemotherapy was of no benefit to patients with unresectable/recurrent GC (N=741) either for overall survival (OS) or progression-free survival (PFS). Tumor specimens prior to chemotherapy were collected for assessing PD-L1 expression for this ancillary study. PD-L1 expression was determined using immunohistochemistry (Dako, 28-8 pharmDx) and used to derive the PD-L1 combined positive score (CPS) and PD-L1 tumor proportion score (TPS). As with the CheckMate 649 study, the cutoff values for PD-L1 CPS and PD-L1 TPS were set at 5 and 1%, respectively. Multivariable analyses were performed using Cox proportional hazard models to evaluate the prognostic significance of PD-L1 CPS and PD-L1 TPS as predictors of OS and PFS. All p values were 2-sided; values <0.05 were considered statistically significant. Results: We analyzed 427 patients with unresectable/recurrent GC. The prevalence of PD-L1 CPS≥5, and PD-L1 TPS≥1% was 33% and 24%, respectively. There was no significant difference in OS and PFS between the PD-L1 CPS ≥5 group and the PD-L1 CPS <5 group (Table). The PD-L1 TPS ≥1% group had superior OS and PFS compared to the PD-L1 TPS <1% group (Table). In multivariable analyses for OS, PD-L1 TPS ≥1% was a significant favorable prognostic factor (hazard ratio (HR) = 0.64 [95% CI: 0.50–0.83], p<0.001), but PD-L1 CPS≥5 was not (HR = 0.82 [95% CI: 0.65–1.02], p = 0.073). In multivariable analyses for PFS, PD-L1 TPS ≥1% was a significant favorable prognostic factor (HR = 0.67 [95% CI: 0.52–0.84], p<0.001), but PD-L1 CPS≥5 was not (HR = 0.83 [95% CI: 0.67–1.03], p = 0.090). Conclusions: PD-L1 TPS≥1% is significantly correlated with longer OS and PFS in patients with unresectable/recurrent GC receiving first-line chemotherapy without ICIs. PD-L1 TPS should be considered as a stratification factor in randomized clinical trials for unresectable/recurrent GC. Clinical trial information: UMIN000007652.
PD-L1 CPS | PD-L1 TPS | |||
---|---|---|---|---|
<5 (N=285) | ≥5 (N=142) | <1% (N=324) | ≥1% (N=103) | |
OS | ||||
Median, mo (95% CI) HR (95% CI), log-rank p | 15.4 (13.7–17.3) – | 15.2 (12.5–17.6) 0.89 (0.71–1.11), 0.299 | 14.6 (13.4–16.5) – | 16.1 (14.8–21.1) 0.74 (0.58–0.95), 0.016 |
PFS | ||||
Median, mo (95% CI) HR (95% CI), log-rank p | 7.2 (5.8–6.5) – | 7.3 (5.8–9.1) 0.94 (0.76–1.16), 0.557 | 7.0 (6.2–7.5) – | 7.9 (6.2–7.9) 0.76 (0.61–0.96), 0.023 |
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