TY - JOUR T1 - Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-001361 VL - 8 IS - 2 SP - e001361 AU - Alessio Cortellini AU - Marco Tucci AU - Vincenzo Adamo AU - Luigia Stefania Stucci AU - Alessandro Russo AU - Enrica Teresa Tanda AU - Francesco Spagnolo AU - Francesca Rastelli AU - Renato Bisonni AU - Daniele Santini AU - Marco Russano AU - Cecilia Anesi AU - Raffaele Giusti AU - Marco Filetti AU - Paolo Marchetti AU - Andrea Botticelli AU - Alain Gelibter AU - Mario Alberto Occhipinti AU - Riccardo Marconcini AU - Maria Giuseppa Vitale AU - Linda Nicolardi AU - Rita Chiari AU - Claudia Bareggi AU - Olga Nigro AU - Alessandro Tuzi AU - Michele De Tursi AU - Nicola Petragnani AU - Laura Pala AU - Sergio Bracarda AU - Serena Macrini AU - Alessandro Inno AU - Federica Zoratto AU - Enzo Veltri AU - Barbara Di Cocco AU - Domenico Mallardo AU - Maria Grazia Vitale AU - David James Pinato AU - Giampiero Porzio AU - Corrado Ficorella AU - Paolo Antonio Ascierto Y1 - 2020/11/01 UR - http://jitc.bmj.com/content/8/2/e001361.abstract N2 - Background Concomitant medications, such as steroids, proton pump inhibitors (PPI) and antibiotics, might affect clinical outcomes with immune checkpoint inhibitors.Methods We conducted a multicenter observational retrospective study aimed at evaluating the impact of concomitant medications on clinical outcomes, by weighing their associations with baseline clinical characteristics (including performance status, burden of disease and body mass index) and the underlying causes for their prescription. This analysis included consecutive stage IV patients with cancer, who underwent treatment with single agent antiprogrammed death-1/programmed death ligand-1 (PD-1/PD-L1) with standard doses and schedules at the medical oncology departments of 20 Italian institutions. Each medication taken at the immunotherapy initiation was screened and collected into key categories as follows: corticosteroids, antibiotics, gastric acid suppressants (including proton pump inhibitors - PPIs), statins and other lipid-lowering agents, aspirin, anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors/Angiotensin II receptor blockers, calcium antagonists, β-blockers, metformin and other oral antidiabetics, opioids.Results From June 2014 to March 2020, 1012 patients were included in the analysis. Primary tumors were: non-small cell lung cancer (52.2%), melanoma (26%), renal cell carcinoma (18.3%) and others (3.6%). Baseline statins (HR 1.60 (95% CI 1.14 to 2.25), p=0.0064), aspirin (HR 1.47 (95% CI 1.04 to 2.08, p=0.0267) and β-blockers (HR 1.76 (95% CI 1.16 to 2.69), p=0.0080) were confirmed to be independently related to an increased objective response rate. Patients receiving cancer-related steroids (HR 1.72 (95% CI 1.43 to 2.07), p<0.0001), prophylactic systemic antibiotics (HR 1.85 (95% CI 1.23 to 2.78), p=0.0030), prophylactic gastric acid suppressants (HR 1.29 (95% CI 1.09 to 1.53), p=0.0021), PPIs (HR 1.26 (95% CI 1.07 to 1.48), p=0.0050), anticoagulants (HR 1.43 (95% CI: 1.16 to 1.77), p=0.0007) and opioids (HR 1.71 (95% CI 1.28 to 2.28), p=0.0002) were confirmed to have a significantly higher risk of disease progression. Patients receiving cancer-related steroids (HR 2.16 (95% CI 1.76 to 2.65), p<0.0001), prophylactic systemic antibiotics (HR 1.93 (95% CI 1.25 to 2.98), p=0.0030), prophylactic gastric acid suppressants (HR 1.29 (95% CI 1.06 to 1.57), p=0.0091), PPI (HR 1.26 (95% CI 1.04 to 1.52), p=0.0172), anticoagulants (HR 1.45 (95% CI 1.14 to 1.84), p=0.0024) and opioids (HR 1.53 (95% CI 1.11 to 2.11), p=0.0098) were confirmed to have a significantly higher risk of death.Conclusion We confirmed the association between baseline steroids administered for cancer-related indication, systemic antibiotics, PPIs and worse clinical outcomes with PD-1/PD-L1 checkpoint inhibitors, which can be assumed to have immune-modulating detrimental effects. ER -