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Predictors of response to immune checkpoint inhibition in a real world gynecologic cancer population.

ABSTRACT: Prognostic factors for immune checkpoint inhibitor (CPI) response in gynecologic cancer are limited. This retrospective study aimed to identify prognostic factors associated with improved overall response rate (ORR) and progression free survival (PFS) in gynecologic cancer patients receiving at least two cycles of CPI. PFS was compared by univariate cox regressions. Univariate and multivariable analyses were used for prognostic factors of PFS and ORR. 72 patients were identified (20 ovarian, 36 endometrial, 13 cervix, 1 vaginal, 2 others). Immune related adverse events (IRAE) occurred in 40.3% of patients (29/72). IRAE was associated with higher ORR (44.8% IRAE vs 20.9% no IRAE, OR 3.1, p = 0.024), improved PFS (12.9 m IRAE vs 4.7 m no IRAE, HR 0.43, p = 0.004) and improved OS (22.9 m IRAE vs 12.2 m no IRAE, HR 0.47, p = 0.021). Additionally, Clear cell histology had superior ORR compared to MSI stable endometrial and ovarian cancers (ORR 57.1% vs 11.8%, OR 10.0, p = 0.032). Responders more often had ARIDIA mutation, PI3K/PTEN alteration and less often had a P53 mutation. In a subset of six MSI-H, recurrent, chemo-naive endometrial cancer ORR was 83.3%. Overall, we found favorable outcomes after CPI for clear cell tumors and patients who developed IRAE. Additionally, first-line systemic therapy with CPI in recurrent MSI-H endometrial cancer had encouraging ORR with durable responses.

SUBMITTER: Kuznicki ML

PROVIDER: S-EPMC7689517 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Predictors of response to immune checkpoint inhibition in a real world gynecologic cancer population.

Kuznicki Michelle L ML Bennett Carrie C Yao Meng M Joehlin-Price Amy A Rose Peter G PG Mahdi Haider H

Gynecologic oncology reports 20201106

Prognostic factors for immune checkpoint inhibitor (CPI) response in gynecologic cancer are limited. This retrospective study aimed to identify prognostic factors associated with improved overall response rate (ORR) and progression free survival (PFS) in gynecologic cancer patients receiving at least two cycles of CPI. PFS was compared by univariate cox regressions. Univariate and multivariable analyses were used for prognostic factors of PFS and ORR. 72 patients were identified (20 ovarian, 36 ...[more]

PMID: 33294575

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Project description:BackgroundFGFR3-altered urothelial cancer (UC) correlates with a non-T cell-inflamed phenotype and has therefore been postulated to be less responsive to immune checkpoint blockade (ICB). Preclinical work suggests FGFR3 signalling may suppress pathways such as interferon signalling that alter immune microenvironment composition. However, correlative studies examining clinical trials have been conflicting as to whether FGFR altered tumours have equivalent response and survival to ICB in patients with metastatic UC. These findings have yet to be validated in real world data, therefore we evaluated clinical outcomes of patients with FGFR3-altered metastatic UC treated with ICB and investigate the underlying immunogenomic mechanisms of response and resistance.Methods103 patients with metastatic UC treated with ICB at a single academic medical center from 2014 to 2018 were identified. Clinical annotation for demographics and cancer outcomes, as well as somatic DNA and RNA sequencing, were performed. Objective response rate to ICB, progression-free survival, and overall survival was compared between patients with FGFR3-alterations and those without. RNA expression, including molecular subtyping and T cell receptor clonality, was also compared between FGFR3-altered and non-altered patients.ResultsOur findings from this dataset confirm that FGFR3-altered (n = 17) and wild type (n = 86) bladder cancers are equally responsive to ICB (12 vs 19%, p = 0.73). Moreover, we demonstrate that despite being less inflamed, FGFR3-altered tumours have equivalent T cell receptor (TCR) diversity and that the balance of a CD8 T cell gene expression signature to immune suppressive features is an important determinant of ICB response.ConclusionsOur work in a real world dataset validates prior observations from clinical trials but also extends this prior work to demonstrate that FGFR3-altered and wild type tumours have equivalent TCR diversity and that the balance of effector T cell to immune suppression signals are an important determinant of ICB response.

Dataset Information

Predictors of response to immune checkpoint inhibition in a real world gynecologic cancer population.

Publications

Predictors of response to immune checkpoint inhibition in a real world gynecologic cancer population.

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