J Rogado1, J M Sánchez-Torres1, N Romero-Laorden1, A I Ballesteros1, V Pacheco-Barcia1, A Ramos-Leví2, R Arranz3, A Lorenzo3, P Gullón4, O Donnay1, M Adrados5, P Costas1, J Aspa6, A Alfranca7, R Mondéjar1, R Colomer8. 1. Medical Oncology Department, Instituto de Investigación Sanitaria la Princesa, HU La Princesa, Madrid, Spain. 2. Endocrinology Department, Instituto de Investigación Sanitaria la Princesa, HU La Princesa, Madrid, Spain. 3. Hematology Department, HU la Princesa, Madrid, Spain. 4. Social and Cardiovascular Epidemiology Research Group, Alcalá University, Madrid, Spain. 5. Pathology Department, Instituto de Investigación Sanitaria La Princesa, HU la Princesa, Madrid, Spain. 6. Neumology Department, Instituto de Investigación Sanitaria La Princesa, HU la Princesa, Madrid, Spain. 7. Immunology Department, Instituto de Investigación Sanitaria la Princesa, Madrid, Spain. 8. Medical Oncology Department, Instituto de Investigación Sanitaria la Princesa, HU La Princesa, Madrid, Spain. Electronic address: rcolomer@seom.org.
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.
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.
Authors: Gino K In; Poorva Vaidya; Alexandra Filkins; David J Hermel; Kevin G King; Omar Ragab; William W Tseng; Mark Swanson; Niels Kokot; Julie E Lang; Lawrence Menendez; Brittney DeClerck; Gene Kim; Jenny C Hu; Alicia Terando; Hossein Jadvar; Charité Ricker; Kimberly A Miller; David H Peng; Ashley Wysong Journal: J Cancer Res Clin Oncol Date: 2020-11-18 Impact factor: 4.553
Authors: Satya Das; Kristen K Ciombor; Sigurdis Haraldsdottir; Yoanna Pumpalova; Ibrahim H Sahin; G Pineda; Yu Shyr; E P Lin; Chih-Yuan Hsu; Shih-Kai Chu; Laura W Goff; Dana B Cardin; Mehmet A Bilen; George A Fisher; Christina Wu; Jordan Berlin Journal: Oncologist Date: 2020-01-14
Authors: Joanna Roopkumar; Shadi Swaidani; Ann S Kim; Bicky Thapa; Lorenzo Gervaso; Brian P Hobbs; Wei Wei; Tyler J Alban; Pauline Funchain; Suman Kundu; Naseer Sangwan; Patricia Rayman; Paul G Pavicic; C Marcela Diaz-Montero; John Barnard; Keith R McCrae; Alok A Khorana Journal: Med (N Y) Date: 2021-03-12