Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice
Year: 2020
Type: article
Study design: Observational Study
Abstract: 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.
Authors: Alessio Cortellini, Marco Tucci, Vincenzo Adamo, Luigia Stefania Stucci, Alessandro Russo, Enrica Teresa Tanda, Francesco Spagnolo, Francesca Rastelli, Renato Bisonni, Daniele Santini, Marco Russano, Cecilia Anesi, Raffaele Giusti, Marco Filetti, Paolo Marchetti, Andrea Botticelli, Alain Gelibter, Mario Alberto Occhipinti, Riccardo Marconcini, Maria Giuseppa Vitale, Linda Nicolardi, Rita Chiari, Claudia Bareggi, Olga Nigro, Alessandro Tuzi, Michele De Tursi, Nicola Petragnani, Laura Pala, Sergio Bracarda, Serena Macrini, Alessandro Inno, Federica Zoratto, Enzo Veltri, Barbara Di Cocco, Domenico Mallardo, Maria Grazia Vitale, David James Pinato, Giampiero Porzio, Corrado Ficorella, Paolo Antonio Ascierto
Institutions: University of L'Aquila, Istituto Tumori Bari, University of Bari Aldo Moro, University of Messina, Ospedale Policlinico San Martino, Università Campus Bio-Medico, Azienda Ospedaliera Sant'Andrea, Policlinico Umberto I, Sapienza University of Rome, Azienda Ospedaliera Universitaria Pisana, Azienda Ospedaliero-Universitaria di Modena, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Ospedale di Circolo e Fondazione Macchi, Aziende Socio Sanitarie Territoriale dei Sette Laghi, University of Chieti-Pescara, European Institute of Oncology, Azienda Ospedaliera S.Maria, Ospedale Sacro Cuore Don Calabria, Ospedale Santa Maria Goretti, Hammersmith Hospital, Imperial College London
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
Award: G2921181837
OpenAlex ID: W3097304584