RT Journal Article
SR Electronic
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
FD BMJ Publishing Group Ltd
SP e001361
DO 10.1136/jitc-2020-001361
VO 8
IS 2
A1 Alessio Cortellini
A1 Marco Tucci
A1 Vincenzo Adamo
A1 Luigia Stefania Stucci
A1 Alessandro Russo
A1 Enrica Teresa Tanda
A1 Francesco Spagnolo
A1 Francesca Rastelli
A1 Renato Bisonni
A1 Daniele Santini
A1 Marco Russano
A1 Cecilia Anesi
A1 Raffaele Giusti
A1 Marco Filetti
A1 Paolo Marchetti
A1 Andrea Botticelli
A1 Alain Gelibter
A1 Mario Alberto Occhipinti
A1 Riccardo Marconcini
A1 Maria Giuseppa Vitale
A1 Linda Nicolardi
A1 Rita Chiari
A1 Claudia Bareggi
A1 Olga Nigro
A1 Alessandro Tuzi
A1 Michele De Tursi
A1 Nicola Petragnani
A1 Laura Pala
A1 Sergio Bracarda
A1 Serena Macrini
A1 Alessandro Inno
A1 Federica Zoratto
A1 Enzo Veltri
A1 Barbara Di Cocco
A1 Domenico Mallardo
A1 Maria Grazia Vitale
A1 David James Pinato
A1 Giampiero Porzio
A1 Corrado Ficorella
A1 Paolo Antonio Ascierto
YR 2020
UL http://jitc.bmj.com/content/8/2/e001361.abstract
AB 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.