Abstract
Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medicationsto create a drug-based prognostic score. We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N=217), and a drug-based prognostic score with the drugs resulting significantly impacting the OSwas computed. Secondly, we externally validated the score in a large multicenter external cohort (n=1012). In the training cohort (n=217), the median age was 69 years (range: 32-89), and the primary tumours were non-small-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR]=2.3; 95% confidence interval [CI]: 1.60-3.30), systemic antibiotics (HR=2.07; 95% CI: 1.31-3.25) and proton-pump inhibitors (PPIs) (HR=1.57; 95% CI: 1.13-2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p<0.0001), PFS(p<0.0001) and ORR(p=0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p<0.0001), PFS (p<0.0001) and ORR (p=0.0006) within the external cohort. Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple scorethat can help stratifying patients in routine practice and clinical trials of ICIs.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
