Dr Thomas on the Predictive Value of IRS For Pembrolizumab Benefit in Advanced Solid Tumors

Sachdev P. Thomas, MD, medical oncologist, Department of Oncology and Hematology, Kaiser Permanente Vallejo Medical Center, discusses the utility of the immunotherapy response score (IRS) when predicting clinical benefit with pembrolizumab (Keytruda) in advanced solid tumors. 

The observational clinical trial (NCT03061305) evaluated whether IRS status could predict responses to pembrolizumab vs previous lines of therapy in patients with advanced solid tumors across the Kaiser Permanente Northern California Health System, Thomas begins.

The IRS is a multivariable biomarker algorithm that combines assessment of tissue-based tumor mutation burden (TMB) with quantitative biomarker expression. The study utilized a crossover design and enrolled patients who had IRS results from 2018 and 2022, as well as tumorspecimens collected between 2011 and 2021. Patients who had electronic health records confirming that they had received more than first-line pembrolizumab monotherapy were also included. Notably, the study excluded individuals with gliomas or prior exposure to immunotherapy.

Time to next treatment (TTNT) was utilized as a real-world progression-free survival end point. TTNT with pembrolizumab was compared with TTNT with the patient's previous line of therapy. Cox proportional hazards models were used to test for an interaction between IRS status and efficacy.

A total of 211 patients were included on the study across multiple tumor types, Thomas states. Of these, 142 had received second-line pembrolizumab and 69 had received third-line pembrolizumab, he expands.

At an estimated median 16 months of follow-up, 36% of patients had a high IRS score, Thomas continues. Results showed that the time to progression or next treatment for IRS-high patients was 20.3 months vs 4.5 months in the IRS-low population, he reports. Ultimately, analysis of this independent dataset confirmed that IRS score is a valid strategy for predicting benefit with pembrolizumab vs prior therapy in solid tumors, and may be a potential biomarker for responses to pembrolizumab monotherapy, Thomas concludes.

Dr Thomas had no relationships to disclose.