Re: Ashley M. Hopkins, Ganessan Kichenadasse, Christos S. Karapetis, et al. Concomitant Proton Pump Inhibitor Use and Survival in Urothelial Carcinoma Treated with Atezolizumab. Clin Cancer Res. In press. https://doi.org/10.1158/1078-0432.CCR-20-1876

Vollständiger Abstract

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<h4>Purpose</h4>POSEIDON (NCT03164616) was a randomized, open-label, multicenter phase 3 trial comparing first-line durvalumab with or without tremelimumab in combination with chemotherapy versus chemotherapy alone in patients with metastatic non-small-cell lung cancer (NSCLC). Overall survival (OS) and progression-free survival were significantly increased in the tremelimumab plus durvalumab and chemotherapy arm. We conducted a post hoc analysis (TRIDENT) to identify patients who may receive greater OS benefit from the addition of tremelimumab to durvalumab and chemotherapy.<h4>Experimental design</h4>This analysis included clinical, genomic, and radiomic data from the POSEIDON trial (data cut-off March 12, 2021). Machine learning models leveraging multimodal data were trained to identify subpopulations of patients that benefit from the addition of tremelimumab to first-line durvalumab and chemotherapy.<h4>Results</h4>Using clinical and genomic data, the model was able to predict treatment benefit from adding tremelimumab to first-line durvalumab and chemotherapy, with the top ranked 50% of patients with non-squamous tumors achieving a HR of 0.56 (95% CI: 0.33-0.97). EGFR wild-type, FGFR3 wild-type, CDKN2A wild-type, KRAS mutations, and STK11 mutations were the factors most associated with higher OS benefit.<h4>Conclusions</h4>By utilizing machine learning models to analyze POSEIDON data, we yielded genetic signatures identifying patients with non-squamous metastatic NSCLC who may derive greater OS benefit from the addition of tremelimumab to first-line durvalumab and chemotherapy. Such approaches could be used in future to enhance precision in tailoring therapies for individual patients.

Abstract: PubMed · Datensatz