PD-L1 Expression Strong Predictor of Overall Survival Benefit From Immune Checkpoint Inhibition in Gastroesophageal Cancer

A systemic review and meta-analysis found that the strongest predictor of overall survival benefit in immune checkpoint inhibition is tissue-based PD-L1 expression — more than any variable aside from microsatellite instability.

Harry Yoon, MD, Mayo Clinic, Rochester, Minnesota, and colleagues wrote, “Whether tissue-based PD-L1 testing is needed to select patients for [immune checkpoint inhibition] has become an area of debate.” They went on to state that while there are exploratory analyses from individual trials indicating a lack of meaningful benefit from immune checkpoint inhibition in patients with absent or low expression of PD-L1, exploratory results should be relied on with extreme caution.

This analysis included 17 phase 3 clinical trials of patients with advanced gastroesophageal cancer, either adenocarcinoma or squamous cell carcinoma, randomized to either anti-PD-1 or PD-L1 containing treatment, compared to standard of care. Of the studies selected, 9 assessed first-line treatments while 8 were after the first line. There were a total of 11,166 participants included.

Of the patients with squamous cell carcinomas (n = 5067), the PD-L1 tumor proportion score was the strongest predictive factor of immune checkpoint inhibition benefit (hazard ratio [HR] 0.60; 95% confidence interval [CI], 0.53 to 0.68 for high tumor proportion score; HR 0.84; 95% CI, 0.75 to 0.95 for low tumor proportion score). The predictive value favoring high tumor proportion score is 41.0%, compared to ≤16.0% for other variables. Of patients with adenocarcinoma, PD-L1 combined positive score was the strongest predictive factor, aside from microsatellite instability high status (HR, 0.73; 95% CI, 0.66 to 0.81 for high combined positive score; HR, 0.95; 95% CI, 0.84 to 1.07 for low combined positive score). The predictive value favoring high combined positive score was 29.4%, compared to ≤12.9% for other variables.

According to Dr Yoon and colleagues, these results “seem to confirm a reduced benefit from [immune checkpoint inhibition] among patients with advanced gastroesophageal cancer and absent or low tissue-based PD-L1 expression.”

Source:

Yoon HH, Jin Z, Kour O, et al. Association of PD-L1 expression and other variables with benefit from immune checkpoint inhibition in advanced gastroesophageal cancer: Systemic review and meta-analysis of 17 phase 3 randomized clinical trials. JAMA Oncol. Published online August 25, 2022. doi: 10.1001/jamaoncol.2022.3707