Comparative outcomes with low-dose and standard-dose immune checkpoint inhibitors in microsatellite stable advanced gastric/gastroesophageal adenocarcinoma

<h3>Background</h3> The combination of chemotherapy and immune checkpoint inhibitors (ICIs) is usually considered standard in advanced gastric/gastroesophageal adenocarcinoma (GC) with combined positive score (CPS) 6≥5. <h3>Methods</h3> Data of patients with microsatellite stable advanced GCs receiving chemotherapy combined with ICIs between August 2021 and February 2024 were collated from eight institutions in India. The primary endpoint was to compare median overall survival between patients receiving standard-dose ICIs (SD-ICIs) and low-dose ICIs (LD-ICIs) as first-line treatment when CPS ≥5. <h3>Results</h3> Data of 288 patients were collated, of whom 256 patients had adequate data for analysis. A CPS ≥5 was seen in 161 patients (63%). Nivolumab was used in a majority of patients (75%). After propensity matching for age, 124 patients (62 patients receiving LD-ICIs and SD-ICIs, each) were available for analysis. With a median follow-up of 9.8 months [95% confidence interval (CI) 7.6-12.1 months], there was no difference in median overall survival between patients receiving LD-ICIs and SD-ICIs (16.8 months, 95% CI 7.59-25.97 months versus 16.1 months, 95% CI 10.3 months-not reached, <i>P</i> = 0.95). There was also no difference in median time to treatment failure between patients receiving LD-ICIs and SD-ICIs (6.83 months, 95% CI 4.65-9.01 months versus 7.78 months, 95% CI 6.04-9.56 months, <i>P</i> = 0.31). <h3>Conclusions</h3> LD-ICIs can be evaluated in combination with chemotherapy in patients with advanced GC and CPS ≥5 where standard dosing is not feasible, pending evidence from prospective trials.