79P - Relevance of combined positive score (CPS) & low-dose immune checkpoint inhibitors (ICIs) in microsatellite stable (MSS) advanced gastric adenocarcinoma (GC): A multi-institution analysis

Background

The combination of chemotherapy and ICIs based on CPS cut-off >=5 is considered standard in advanced GCs. There is emerging data on the use of low dose (LD) ICIs in multiple cancers.

Methods

Data of patients with MSS advanced GCs receiving chemotherapy combined with ICIs between August 2021 and February 2024 was collated from eight institutions in India. The co-primary endpoints of the study were to identify the predictive value of a CPS cutoff >=5 [using Ventana SP263 or the Dako PD-L1 22C3 assay) being statistically significant in predicting for improved median OS and to compare median OS between patients receiving standard dose ICIs (SD-ICI) and LD-ICIs in patients with CPS >=5. Median OS was computed by Kaplan-Meier method.

Results

A total of 262 patients were available for analysis during the study period. The majority of patients received ICIs during second line therapy or beyond as opposed to first line therapy (148, 56% vs 114, 44%), with 201 patients (77%) receiving nivolumab (SD – 94, LD – 107) and 61 patients (23%) receiving pembrolizumab (SD-60; LD-1). With a median follow up of 12.5 months [95% Confidence interval (CI): 9.4-15.6], the median OS of the entire cohort was 14.4 months (95% CI: 10.3-18.6). The CPS cutoff >=5 (n=163) did not achieve statistical significance in predicting for improved OS compared to CPS<5 (n=99), during 1^st line therapy (p=0.46) and or during later lines therapy (p=0.062). In patients with CPS>=5 (n=163), there was no significant differences in median OS in patients receiving LD-ICI (n=78) as compared to SD-ICI (n=85) (14.1 months vs. 16.1 months; p=0.95). No differences in OS were seen between the LD-ICI and SD-ICI cohorts, whether used initially or during later lines of therapy (p=0.988).

Conclusions

The use of a CPS cutoff >=5 for predicting outcomes in MSS advanced gastric adenocarcinomas probably needs to be standardized with respect to various platforms and re-visited for relevance in real world practice. Low dose immune checkpoint inhibitors can be evaluated in combination with chemotherapy in patients where standard dosing is not feasible due to logistics, pending evidence from prospective trials.

Legal entity responsible for the study

Tata Memorial Centre, Mumbai.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.