Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients.

Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of anti-PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy. We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer. irAEs (immune-related adverse events) were identified clinically and graded as per the Common Terminology Criteria for Adverse Events version 4.0. Efficacy was evaluated with objective response rate (ORR, immune-Response Evaluation Criteria in Solid Tumours [RECIST] criteria) progression-free survival (PFS) and overall survival (OS). Tests were performed to determine the association between irAEs and ORR, PFS or OS. We identified 106 patients. Primary diagnoses were lung cancer (n = 77), melanoma (n = 8), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma (n = 1 each). IrAEs were observed in 40 patients (37.7%). The most frequent irAEs were hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 44 patients (41.5%), and median PFS was 5.5 months (0.5-31 months). Thirty-three of the 40 patients with irAEs had objective response (82.5%) in contrast with 11 of the 66 cases without irAEs (16.6%) (OR 23.5, P < 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without irAEs (HR 2.2, P = 0.016). OS in patients with irAEs was 32 months and 22 in those without irAEs, without statistically significant differences. In advanced cancer treated with single-agent anti-PD-1 antibodies, patients with irAEs showed a markedly improved efficacy over patients without irAEs (ORR of 82.5% and PFS of 10 months vs ORR of 16.6% and PFS of 3 months). Future studies of anti-PD-1 immune-therapy should address this association to explore the underlying biological mechanisms of efficacy.

Rogado J ，Sánchez-Torres JM ，Romero-Laorden N ，Ballesteros AI ，Pacheco-Barcia V ，Ramos-Leví A ，Arranz R ，Lorenzo A ，Gullón P ，Donnay O ，Adrados M ，Costas P ，Aspa J ，Alfranca A ，Mondéjar R ，Colomer R ... -  《-》

Profiling Preexisting Antibodies in Patients Treated With Anti-PD-1 Therapy for Advanced Non-Small Cell Lung Cancer.

Toi Y ，Sugawara S ，Sugisaka J ，Ono H ，Kawashima Y ，Aiba T ，Kawana S ，Saito R ，Aso M ，Tsurumi K ，Suzuki K ，Shimizu H ，Domeki Y ，Terayama K ，Nakamura A ，Yamanda S ，Kimura Y ，Honda Y ... -  《-》

Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients.

Immune-related adverse events (irAEs) developed during immunotherapy with anti-PD-1 agents, could be a predictive surrogate marker of clinical benefit in patients with advanced non-small-cell lung cancer (NSCLC). Patients with NSCLC, treated with anti-PD-1 agents, were retrospectively evaluated. Univariate and multivariate analyses were performed to evaluate the relationships between types of irAEs (differentiated according to system/organ involved and to single-site/multiple-site), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). We further performed a 6-week landmark analysis. A total of 559 patients were enrolled; 231 patients (41.3%) developed irAEs of any grade and 50 patients (8.9%) G3/G4 events; 191 of them (82.6%) developed "single-site" irAEs and 40 (17.4%) "multiple-site" irAEs. At multivariate analysis, higher ORR was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), endocrine (P = .0043) and skin irAEs (P = .0005). Longer PFS was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), "multiple-site" irAEs (P = .0374), endocrine irAEs (P = .0084) and skin irAEs (P = .0001). Longer OS was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), endocrine irAEs (P = .0044), gastrointestinal irAEs (P = .0437), skin irAEs (P = .0006), and others irAEs (P = .0378). At the 6-week landmark analysis, irAEs of any grade was confirmed an independent predictor of higher ORR, longer PFS, and longer OS. Our study confirmed that irAEs are concordantly related to higher ORR, longer PFS, and longer OS with anti-PD-1 immunotherapy in patients with NSCLC.

Cortellini A ，Chiari R ，Ricciuti B ，Metro G ，Perrone F ，Tiseo M ，Bersanelli M ，Bordi P ，Santini D ，Giusti R ，Grassadonia A ，Di Marino P ，Tinari N ，De Tursi M ，Zoratto F ，Veltri E ，Malorgio F ，Garufi C ，Russano M ，Anesi C ，Zeppola T ，Filetti M ，Marchetti P ，Berardi R ，Rinaldi S ，Tudini M ，Silva RR ，Pireddu A ，Atzori F ，Iacono D ，Migliorino MR ，Porzio G ，Cannita K ，Ficorella C ，Buti S ... -  《-》

Correlation between immune-related adverse events and prognosis in patients with various cancers treated with anti PD-1 antibody.

Matsuoka H ，Hayashi T ，Takigami K ，Imaizumi K ，Shiroki R ，Ohmiya N ，Sugiura K ，Kawada K ，Sawaki A ，Maeda K ，Ando Y ，Uyama I ... -  《BMC CANCER》

Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab.

Masuda K ，Shoji H ，Nagashima K ，Yamamoto S ，Ishikawa M ，Imazeki H ，Aoki M ，Miyamoto T ，Hirano H ，Honma Y ，Iwasa S ，Okita N ，Takashima A ，Kato K ，Boku N ... -  《BMC CANCER》