This ancillary analysis used pretreatment tumor specimens from the phase III randomized trial JCOG1013 to evaluate the prognostic significance of PD-L1 expression in patients with chemotherapy‑naive unresectable or recurrent gastric cancer. PD-L1 expression was measured with the Dako 28-8 pharmDx assay. Both the combined positive score (CPS) and the tumor proportion score (TPS) were calculated from these specimens. PD-L1 positivity was defined a priori as CPS ≥ 5 or TPS ≥ 1%.
Out of 741 patients enrolled in JCOG1013, 540 patients had PD-L1 assessment available and were included in this analysis. The parent trial randomized patients with unresectable or recurrent gastric cancer who were 20–75 years old and had HER2‑negative or unknown HER2 status; JCOG1013 itself compared docetaxel/cisplatin/S-1 versus cisplatin/S-1 in the first‑line setting and showed no OS or PFS benefit for the triplet regimen.
In univariable analyses reported in the source excerpt, neither CPS ≥ 5 nor TPS ≥ 1% was significantly associated with overall survival (OS) or progression‑free survival (PFS).
In multivariable analyses, results diverged between the two PD-L1 scoring systems. CPS ≥ 5 was not significantly associated with OS (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.71–1.04; p = 0.127) or PFS (HR 0.92, 95% CI 0.77–1.11; p = 0.392).
By contrast, TPS ≥ 1% was significantly associated with improved outcomes after adjustment: OS HR 0.78 (95% CI 0.62–0.97; p = 0.028) and PFS HR 0.76 (95% CI 0.62–0.94; p = 0.012). The authors therefore identify TPS ≥ 1% as an independent favorable prognostic factor for survival among patients receiving chemotherapy alone.
These findings indicate that PD-L1 expression assessed by TPS ≥ 1% — but not CPS ≥ 5 — had independent prognostic value in this cohort treated without immune checkpoint inhibitors (ICIs). The result is noteworthy in the current therapeutic landscape where first‑line treatment of unresectable or recurrent HER2‑negative gastric cancer increasingly incorporates ICIs plus chemotherapy and where PD-L1 CPS has been used as a predictive companion/complementary marker to guide ICI use.
The ancillary analysis suggests that PD-L1 expression on tumor cells (as captured by TPS) may carry prognostic information even when ICIs are not used. In clinical practice, CPS remains a commonly reported metric to select patients for PD‑1 axis inhibitors, and CPS thresholds (for example CPS ≥ 5) have been discussed in meta-analyses as optimizing risk–benefit in ICI-containing regimens. Nevertheless, chemotherapy alone continues to be an important option for patients with low CPS, particularly CPS < 1.
Gastric cancer remains a major global cause of cancer mortality, with particularly high prevalence and burden in East Asia. Historically, platinum plus fluoropyrimidine doublets have been the backbone of first‑line chemotherapy for unresectable or recurrent HER2‑negative disease. The parent randomized trial, JCOG1013, found no survival benefit from adding docetaxel to cisplatin/S-1.
The advent of PD‑1/PD‑L1 inhibition combined with chemotherapy in first‑line treatment has changed the standard of care in many settings. PD-L1 expression, evaluated as CPS or TPS, was used in pivotal trials as a predictive biomarker for PD‑1 inhibitors. However, the prognostic meaning of PD-L1 expression in patients treated with chemotherapy without ICIs has been inconsistent across studies, likely due to differences in patient populations, PD-L1 assays and scoring systems, cut-offs, and inter-observer variability in pathology interpretation.
This ancillary study was undertaken to clarify the prognostic impact of PD-L1 status specifically in patients with unresectable or recurrent gastric cancer receiving first‑line chemotherapy without ICIs.
PD-L1 was assessed using the Dako 28-8 pharmDx immunohistochemistry assay on pretreatment tumor samples. The study calculated both the combined positive score (CPS), which incorporates PD-L1 staining in tumor and immune cells, and the tumor proportion score (TPS), which reflects PD-L1 expression on tumor cells alone. PD-L1 positivity was predefined as CPS ≥ 5 or TPS ≥ 1%.
Univariable and multivariable statistical analyses were performed for OS and PFS. The provided excerpt reports hazard ratios, 95% confidence intervals, and p values for the associations of CPS ≥ 5 and TPS ≥ 1% with survival outcomes; however, the excerpt does not list all covariates included in the multivariable models or the modeling strategy in full detail.
The source excerpt documents primary results but omits several methodological and descriptive details. Specifically, the excerpt does not report the full set of baseline characteristics for the 540 patients included, the exact covariates entered into the multivariable models, the number of events, methods for handling missing data, subgroup or sensitivity analyses, or detailed assay performance metrics (for example, inter‑observer reproducibility). Consequently, further methodological and numerical detail is not available from the provided text.
In this ancillary analysis of JCOG1013, TPS ≥ 1% was identified as an independent favorable prognostic factor for overall and progression‑free survival in patients with unresectable or recurrent gastric cancer treated with first‑line chemotherapy without ICIs. CPS ≥ 5 was not independently associated with improved OS or PFS in adjusted analyses. The clinical trial registration number for JCOG1013 is UMIN000007652.
Note: additional methodological and result details beyond those summarized above were not reported in the provided source excerpt and therefore are not included here.