Immune-related adverse events predict the therapeutic efficacy of anti–PD-1 antibodies in cancer patients. (March 2019)

• Record Type: Journal Article
• Authors: Rogado, J.; Sánchez-Torres, J.M.; Romero-Laorden, N.; Ballesteros, A.I.; 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.
• Is Part Of: European journal of cancer. Volume 109(2019)
• Page Start: 21
• Page End: 27
• Publication Date: 2019-03
• Subjects: Immune-related adverse events -- Nivolumab -- Pembrolizumab -- Advanced cancer -- Response predictive factor; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.10.014
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: 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. Patients and methods: 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. Results: 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. Conclusion: 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. Highlights: In advanced cancer treated with anti–PD-1 antibodies nivolumab or pembrolizumab, incidence of irAEs was associated with a marked efficacy. Response rate increased significantly from 16.6% to 82.5% when an irAE was present. The follow-up showed an increase of PFS from 3 to 10 months when an irAE was present. The follow-up showed an increase of OS from 22 to 32 months when an irAE was present.