Emily Hinchcliff1, David Hong2, Hung Le2, Gary Chisholm3, Revathy Iyer4, Aung Naing2, Patrick Hwu5, Amir Jazaeri3. 1. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America. Electronic address: emhinchcliff@mdanderson.org. 2. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America. 3. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America. 4. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America. 5. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
Abstract
OBJECTIVE: To describe the clinical outcomes associated with the use of checkpoint inhibitor therapy in recurrent ovarian malignancy. METHODS: Women with recurrent ovarian cancer treated with an immune checkpoint inhibitor between 1/2012 and 8/2017 were included. RECIST criteria determined disease status, and immune related adverse events (irAE) were graded per trial protocols. Predictors of response, irAE, progression free survival (PFS) and overall survival (OS) were investigated. RESULTS: Forty-four women were included with a median age of 53 years, median of 4 prior lines of chemotherapy, and most commonly high grade serous pathology (59.1%). 3 patients had partial response and 3 had pseudoprogression, for a response rate of 14.2%. In subset analysis of high grade serous (HGSOC) pathology, platinum sensitivity at time of checkpoint inhibitor therapy was correlated with response (p = 0.01). There were 28 grade 3/4 irAEs in 21 patients (47.7%). Combination therapy rather than monotherapy predicted irAE (OR 5.7, CI 1.6-20.9, p = 0.02). The most common severe irAE was elevation in hepatic or pancreatic enzymes in 12 total patients (13.6% each). Interestingly, the number of genes mutated was protective from hepatic/pancreatic AE (p = 0.02). CONCLUSIONS: While response rate was similar to prior literature, in patients with HGSOC platinum sensitivity at time of checkpoint inhibitor initiation was correlated to response. Grade 3/4 hepatic and pancreatic enzyme elevations were more common in ovarian cancer patients than has been previously reported in other tumor types. The number of genes mutated was inversely correlated to risk of this type of irAEs but not to total irAEs.
OBJECTIVE: To describe the clinical outcomes associated with the use of checkpoint inhibitor therapy in recurrent ovarian malignancy. METHODS:Women with recurrent ovarian cancer treated with an immune checkpoint inhibitor between 1/2012 and 8/2017 were included. RECIST criteria determined disease status, and immune related adverse events (irAE) were graded per trial protocols. Predictors of response, irAE, progression free survival (PFS) and overall survival (OS) were investigated. RESULTS: Forty-four women were included with a median age of 53 years, median of 4 prior lines of chemotherapy, and most commonly high grade serous pathology (59.1%). 3 patients had partial response and 3 had pseudoprogression, for a response rate of 14.2%. In subset analysis of high grade serous (HGSOC) pathology, platinum sensitivity at time of checkpoint inhibitor therapy was correlated with response (p = 0.01). There were 28 grade 3/4 irAEs in 21 patients (47.7%). Combination therapy rather than monotherapy predicted irAE (OR 5.7, CI 1.6-20.9, p = 0.02). The most common severe irAE was elevation in hepatic or pancreatic enzymes in 12 total patients (13.6% each). Interestingly, the number of genes mutated was protective from hepatic/pancreatic AE (p = 0.02). CONCLUSIONS: While response rate was similar to prior literature, in patients with HGSOC platinum sensitivity at time of checkpoint inhibitor initiation was correlated to response. Grade 3/4 hepatic and pancreatic enzyme elevations were more common in ovarian cancerpatients than has been previously reported in other tumor types. The number of genes mutated was inversely correlated to risk of this type of irAEs but not to total irAEs.
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