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Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials.

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.

SUBMITTER: Hinchcliff E

PROVIDER: S-EPMC6281778 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials.

Hinchcliff Emily E Hong David D Le Hung H Chisholm Gary G Iyer Revathy R Naing Aung A Hwu Patrick P Jazaeri Amir A

Gynecologic oncology 20181024 3

<h4>Objective</h4>To describe the clinical outcomes associated with the use of checkpoint inhibitor therapy in recurrent ovarian malignancy.<h4>Methods</h4>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. ...[more]

PMID: 30366646

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Project description:BackgroundImmune checkpoint inhibitor (ICI)-induced pancreatic injury (ICIPI) is not well documented in the literature. We aimed to describe the clinical characteristics and outcomes of patients who developed ICIPI.MethodsWe reviewed the medical records of consecutive patients who had a confirmed diagnosis of ICIPI (Common Terminology Criteria for Adverse Events grade ≥ 3 lipase elevation with or without clinical symptoms) from April 2011 through April 2018.ResultsAmong the 2,279 patients received ICI and had lipase values checked thereafter, 82 (4%) developed ICIPI. Overall, 65% of patients received inhibitors of programmed death protein-1 or its ligand. Compared with asymptomatic presentation, patients who had clinical symptoms of pancreatitis (n = 32) had higher levels of lipase (P = 0.032), more frequent imaging evidence of pancreatitis (P = 0.055), and more frequent hospitalization (P < 0.001) and received intravenous fluids (P < 0.001) and steroids more frequently (P = 0.008). Twelve patients (15%) developed long-term adverse outcomes of ICIPI; three had chronic pancreatitis, four had recurrence of ICIPI, and six had subsequent diabetes. Among 35 patients who resumed ICI therapy, four (11%) had recurrence of lipase elevation. Logistic regression revealed that smoking and hyperlipidemia were associated with increased risk for long-term adverse outcomes of ICIPI, and intravenous fluids were associated with reduced risk. Patients who resumed ICI therapy survived longer than patients who discontinued ICI therapy permanently, statistically not significant (P = 0.0559). Patients who developed long-term adverse outcomes of ICIPI survived significantly longer than those who did not (P = 0.0295). The highest proportion of patients (6/21, 29%) developed long-term adverse outcomes of ICIPI was among those without typical symptoms of pancreatitis, continued ICI therapy after ICIPI, and did not receive intravenous fluids.ConclusionICIPI can present as typical acute pancreatitis, with risk of the development of a pseudocyst, diabetes, and chronic pancreatitis. ICI resumption after ICIPI may lead to recurrence of lipase elevation without increased risk of long-term adverse outcomes, and can increase survival duration. Intravenous fluids may prevent long-term adverse outcomes, but steroids do not appear to affect outcomes of ICIPI. Asymptomatic ICIPI presentation may lead to undertreatment of ICIPI owing to underestimation of its degree, and therefore, intravenous fluid administration could potentially could potentially be benificial to prevent long-term adverse outcomes even in asymptomatic patients.

Project description:BackgroundIn the current study, the authors assessed the risks and outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with resolved grade 3 to 4 ICI hepatitis because current guidelines recommend permanent ICI discontinuation in these patients.MethodsThe authors performed a retrospective cohort study from 2010 through 2019 of patients with melanoma who were treated with ≥1 ICIs and who recovered from grade 3 to 4 ICI hepatitis. The primary outcome was hepatitis recurrence and the secondary outcome was the development of any immune-related adverse event (irAE) requiring the discontinuation of ICI rechallenge. Best overall response and time to all-cause death were compared between the patients who did and those who did not undergo ICI rechallenge. Grading was performed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).ResultsOf the 102 patients with melanoma who developed high-grade ICI hepatitis, 31 underwent ICI rechallenge. Although 15 of 31 patients (48%) developed an irAE of any grade, only 6 patients (19%) required ICI discontinuation due to irAE severity (4 of 29 patients [14%] rechallenged with anti-PD-1 or anti-PD-L1 and 2 of 2 patients [100%] rechallenged with ipilimumab). Recurrent hepatitis accounted for 4 of these 6 cases. Rechallenged patients who did not require ICI discontinuation were found to be significantly less likely to receive ipilimumab rather than anti-PD-1 or anti-PD-L1 monotherapy (0% vs 33%; relative risk (RR), 0.1 [95% CI, 0.1-0.3; P = .032]) and significantly less likely to be rechallenged with their original ICI (8% vs 50%; RR, 0.2 [95% CI, 0.1-0.7; P = .038]). There was no difference noted with regard to best overall response or time to death between rechallenged and non-rechallenged patients.ConclusionsICI therapy can be resumed in patients with melanoma who have recovered from grade 3 to 4 ICI hepatitis with a modest risk of serious irAEs. It remains unclear whether ICI retreatment improves clinical outcomes.

Dataset Information

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials.

Publications

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials.

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