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
- Creators
- Buti S.
- Bersanelli M.
- Perrone F.
- Tiseo M.
- Tucci M.
- Adamo V.
- Stucci L. S.
- Russo A.
- Tanda E. T.
- Spagnolo F.
- Rastelli F.
- Pergolesi F.
- Santini D.
- Russano M.
- Anesi C.
- Giusti R.
- Filetti M.
- Marchetti P.
- Botticelli A.
- Gelibter A.
- Occhipinti M. A.
- Ferrari M.
- Vitale M. G.
- Nicolardi L.
- Chiari R.
- Rijavec E.
- Nigro O.
- Tuzi A.
- De Tursi M.
- Di Marino P.
- Conforti F.
- Queirolo P.
- Bracarda S.
- Macrini S.
- Gori S.
- Zoratto F.
- Veltri E.
- Di Cocco B.
- Mallardo D.
- Vitale M. G.
- Santoni M.
- Patruno L.
- Porzio G.
- Ficorella C.
- Pinato D. J.
- Ascierto P. A.
- Cortellini A.
- Others:
- Buti, S.
- Bersanelli, M.
- Perrone, F.
- Tiseo, M.
- Tucci, M.
- Adamo, V.
- Stucci, L. S.
- Russo, A.
- Tanda, E. T.
- Spagnolo, F.
- Rastelli, F.
- Pergolesi, F.
- Santini, D.
- Russano, M.
- Anesi, C.
- Giusti, R.
- Filetti, M.
- Marchetti, P.
- Botticelli, A.
- Gelibter, A.
- Occhipinti, M. A.
- Ferrari, M.
- Vitale, M. G.
- Nicolardi, L.
- Chiari, R.
- Rijavec, E.
- Nigro, O.
- Tuzi, A.
- De Tursi, M.
- Di Marino, P.
- Conforti, F.
- Queirolo, P.
- Bracarda, S.
- Macrini, S.
- Gori, S.
- Zoratto, F.
- Veltri, E.
- Di Cocco, B.
- Mallardo, D.
- Vitale, M. G.
- Santoni, M.
- Patruno, L.
- Porzio, G.
- Ficorella, C.
- Pinato, D. J.
- Ascierto, P. A.
- Cortellini, A.
Description
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.
Additional details
- URL
- https://hdl.handle.net/11567/1183321
- URN
- urn:oai:iris.unige.it:11567/1183321
- Origin repository
- UNIGE