Impact of PD-L1 expression on survival in patients with unresectable/recurrent gastric cancer receiving first-line chemotherapy without immune checkpoint inhibitors.

Authors

null

Hidekazu Hirano

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

Organizations

National Cancer Center Hospital, Tokyo, Japan, National Center for Global Health and Medicine, Tokyo, Japan, Keio University Hospital, Tokyo, Japan, Saitama Cancer Center, Saitama, Japan, Kitasato University Hospital, Sagamihara-Shimi-Ku Mina, Japan, Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan, Kanagawa Cancer Center, Yokohama, Japan, National Cancer Center Hospital East, Kashiwa, Japan, Kyoto Medical Center, Kyoto, Japan, Kindai University Faculty of Medicine, Osaka-Sayama, Japan, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, School of Medicine, Wakayama Medical University, Wakayama-Shi, Japan, Aichi Cancer Center Hospital, Nagoya, Japan, Osaka University Graduate School of Medicine, Suita, Japan, Shizuoka Cancer Center, Nagaizumi, Japan

Research Funding

No funding sources reported

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.

Efficacy based on PD-L1 expression.

PD-L1 CPSPD-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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Abstract Details

Meeting

2024 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers

Track

Esophageal and Gastric Cancer,Other GI Cancer

Sub Track

Tumor Biology, Biomarkers, and Pathology

Clinical Trial Registration Number

UMIN000007652

Citation

J Clin Oncol 42, 2024 (suppl 3; abstr 391)

DOI

10.1200/JCO.2024.42.3_suppl.391

Abstract #

391

Poster Bd #

J14

Abstract Disclosures