Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index

Sebastiano Buti, Melissa Bersanelli, Fabiana Perrone, Marcello Tiseo, Marco Tucci, Vincenzo Adamo, Luigia S. Stucci, Alessandro Russo, Enrica T. Tanda, Francesco Spagnolo, Francesca Rastelli, Federica Pergolesi, Daniele Santini, Marco Russano, Cecilia Anesi, Raffaele Giusti, Marco Filetti, Paolo Marchetti, Andrea Botticelli, Alain GelibterMario Alberto Occhipinti, Marco Ferrari, Maria Giuseppa Vitale, Linda Nicolardi, Rita Chiari, Erika Rijavec, Olga Nigro, Alessandro Tuzi, Michele De Tursi, Pietro Di Marino, Fabio Conforti, Paola Queirolo, Sergio Bracarda, Serena Macrini, Stefania Gori, Federica Zoratto, Enzo Veltri, Barbara Di Cocco, Domenico Mallardo, Maria Grazia Vitale, Matteo Santoni, Leonardo Patruno, Giampiero Porzio, Corrado Ficorella, David J. Pinato, Paolo A. Ascierto, Alessio Cortellini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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 medications to create a drug-based prognostic score. Methods: 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 OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012). Results: 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. Conclusion: Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs.

Original languageEnglish
Pages (from-to)18-28
Number of pages11
JournalEuropean Journal of Cancer
Volume142
DOIs
Publication statusPublished - Jan 2021

Keywords

  • Antibiotics
  • Cancer patients
  • Concomitant medications
  • Corticosteroids
  • Drugs
  • Immune checkpoint inhibitors
  • Immunotherapy
  • Index
  • Prognostic
  • Proton-pump inhibitors
  • Score

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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