Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice

被引：201

作者：

Cortellini, Alessio ^{[1
,2
]}

Tucci, Marco ^{[3
,4
]}

Adamo, Vincenzo ^{[5
]}

Stucci, Luigia Stefania ^{[3
]}

Russo, Alessandro ^{[5
]}

Tanda, Enrica Teresa ^{[6
]}

Spagnolo, Francesco ^{[6
]}

Rastelli, Francesca ^{[7
]}

Bisonni, Renato ^{[7
]}

Santini, Daniele ^{[8
]}

Russano, Marco ^{[8
]}

Anesi, Cecilia ^{[8
]}

Giusti, Raffaele ^{[9
]}

Filetti, Marco ^{[9
]}

Marchetti, Paolo ^{[9
,10
,11
]}

Botticelli, Andrea ^{[10
]}

Gelibter, Alain ^{[11
]}

Occhipinti, Mario Alberto ^{[11
]}

Marconcini, Riccardo ^{[12
]}

Vitale, Maria Giuseppa ^{[13
]}

Nicolardi, Linda ^{[14
]}

Chiari, Rita ^{[14
]}

Bareggi, Claudia ^{[15
]}

Nigro, Olga ^{[16
]}

Tuzi, Alessandro ^{[16
]}

De Tursi, Michele ^{[17
]}

Petragnani, Nicola ^{[18
]}

Pala, Laura ^{[19
]}

Bracarda, Sergio ^{[20
]}

Macrini, Serena ^{[20
]}

Inno, Alessandro ^{[21
]}

Zoratto, Federica ^{[22
]}

Veltri, Enzo ^{[22
]}

Di Cocco, Barbara ^{[22
]}

Mallardo, Domenico ^{[23
]}

Vitale, Maria Grazia ^{[23
]}

Pinato, David James ^{[24
]}

Porzio, Giampiero ^{[2
]}

Ficorella, Corrado ^{[1
,2
]}

Ascierto, Paolo Antonio ^{[23
]}

机构：

[1] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Laquila, Italy

[2] Salvatore Hosp, Med Oncol, Laquila, Italy

[3] Univ Bari, Dept Biomed Sci & Human Oncol, Med Oncol Unit, Bary, Italy

[4] Tumori Inst IRCCS Giovanni Paolo II, Natl Canc Res Ctr, Bari, Italy

[5] Univ Messina, Dept Human Pathol, Med Oncol, AO Papardo, Messina, Italy

[6] IRCCS Osped Policlin San Martino, Genoa, Italy

[7] ASUR Dist Area 4 Fermo, Med Oncol, Fermo, Italy

[8] Campus Biomed Univ, Med Oncol, Rome, Italy

[9] St Andrea Hosp Rome, Med Oncol Unit, Rome, Italy

[10] Sapienza Univ Rome, Dept Clin & Mol Med, Rome, Italy

[11] Sapienza Univ Rome, Med Oncol Unit B, Policlin Umberto 1, Rome, Italy

[12] Azienda Osped Univ Pisana, Med Oncol, Pisa, Italy

[13] Univ Hosp Modena, Med Oncol, Modena, Italy

[14] Azienda ULSS 6 Euganea, UOC Oncol Padova Sud, Padua, Italy

[15] Fdn IRCCS Ca Granda Osped Maggiore Milano Policli, Med Oncol Unit, Milan, Italy

[16] Osped Circolo & Fdn Macchi, Med Oncol, ASST Sette Laghi, Varese, Italy

[17] Gabriele dAnnunzio Univ Chieti & Pescara, Dept Med Oral & Biotechnol Sci, Chieti, Italy

[18] Univ G DAnnunzio Chieti & Pescara, Dept Psychol Hlth & Terr Sci, Chieti, Italy

[19] IEO European Inst Oncol IRCCS, Div Med Oncol Melanoma, Sarcoma & Rare Tumors, Milan, Italy

[20] Azienda Osped S Maria, Med Oncol, Terni, Italy

[21] IRCCS Osped Sacro Cuore Don Calabria, Oncol Unit, Negrar, Italy

[22] Santa Maria Goretti Hosp, Med Oncol, Latina, Italy

[23] Ist Nazl Tumori IRCCS Fdn G Pascale, Melanoma Canc Immunotherapy & Dev Therapeut Unit, Naples, Italy

[24] Imperial Coll London, Hammersmith Hosp, Dept Surg & Canc, Div Canc, London, England

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2020年 / 8卷 / 02期

基金：

英国惠康基金;

关键词：

immunotherapy; PROTON PUMP INHIBITORS; ELDERLY-PATIENTS; GUT MICROBIOME; CANCER; CHOLESTEROL; ASPIRIN; ANTIBIOTICS; ASSOCIATION; METASTASIS; MELANOMA;

D O I：

10.1136/jitc-2020-001361

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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, beta-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 beta-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.

引用

页数：16

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