Dataset Information

An Exceptional Response to Dostarlimab in Mismatch Repair Deficient, Microsatellite Instability-High and Platinum Refractory Endometrial Cancer.

ABSTRACT: Until recently, effective therapies for advanced endometrial cancer progressing to a platinum-based combination were lacking. In this setting, immunotherapy with anti PD-1/PDL-1 monoclonal antibodies is rising as a new paradigm in particular for patients with microsatellites instability/mismatch repair deficiency. In this case report, we describe an exceptional and rapid response to dostarlimab in a platinum refractory endometrial cancer patient with high disease burden harboring a mismatch repair deficiency.

SUBMITTER: Bartoletti M

PROVIDER: S-EPMC9332114 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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An Exceptional Response to Dostarlimab in Mismatch Repair Deficient, Microsatellite Instability-High and Platinum Refractory Endometrial Cancer.

Bartoletti Michele M Giorda Giorgio G Viel Alessandra A Fornasarig Mara M Zdjelar Adrian A Segatto Enrica E Sorio Roberto R Corsetti Serena S Scalone Simona S Nicoloso Milena Sabrina MS Pivetta Tania T Lucia Emilio E Clemente Nicolò N Palazzari Elisa E Canzonieri Vincenzo V Puglisi Fabio F

Current oncology (Toronto, Ont.) 20220722 8

Until recently, effective therapies for advanced endometrial cancer progressing to a platinum-based combination were lacking. In this setting, immunotherapy with anti PD-1/PDL-1 monoclonal antibodies is rising as a new paradigm in particular for patients with microsatellites instability/mismatch repair deficiency. In this case report, we describe an exceptional and rapid response to dostarlimab in a platinum refractory endometrial cancer patient with high disease burden harboring a mismatch repa ...[more]

PMID: 35892982

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Project description:ObjectiveThere is an increase in patient-reported outcome assessments to gain information on new drug candidates from the patient's perspective. A data gap remains in patient-reported outcome measurements for anti-programmed death 1 (anti-PD-1) therapies in endometrial cancer. We present patient-reported outcome measures collected from patients with mismatch repair-deficient/microsatellite instability-high advanced or recurrent endometrial cancer treated with dostarlimab, an anti-PD-1 monoclonal antibody, in an expansion cohort of the GARNET trial.MethodsGARNET (NCT02715284) is a phase I single-arm study of dostarlimab monotherapy in multiple tumor types. Patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer were treated with 500 mg of intravenous dostarlimab once every 3 weeks for four cycles, then 1000 mg of intravenous dostarlimab every 6 weeks. Patient-reported outcome assessments were an exploratory endpoint, measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30).ResultsAt data cut-off, 88 patients with mismatch repair-deficient endometrial cancer were included in the analysis. Patient-reported outcome assessment completion was >95.5% throughout cycle 7 of the trial, with no individual domain completion <90.9%. Quality of life, emotional functioning, and social functioning showed improvement compared with baseline. All symptom scores showed either improvement or stability from baseline through cycle 7. Categorical change in response across all symptom scales and single-item response scores showed stability or improvement for most patients. For patients who saw a worsening of their categorical change in response, ≤7.4% experienced a 2-category worsening and ≤2.5% experienced a 3-category worsening.ConclusionsMost patients remained stable or had improved quality of life while receiving dostarlimab for the treatment of recurrent or advanced mismatch repair-deficient endometrial cancer.Trial registration numberNCT02715284.

Project description:PurposeKEYNOTE-164 (NCT02460198) evaluated the antitumor activity of pembrolizumab in previously treated, metastatic, microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC).MethodsThis phase II open-label study involved 128 centers worldwide. Eligible patients were age ≥ 18 years and had metastatic MSI-H/dMMR CRC treated with ≥ 2 prior lines of standard therapy, including fluoropyrimidine, oxaliplatin, and irinotecan with or without anti-vascular endothelial growth factor/epidermal growth factor receptor monoclonal antibody (cohort A) or ≥ 1 prior line of therapy (cohort B). MSI-H/dMMR status was assessed locally. Patients received pembrolizumab 200 mg every 3 weeks for up to 2 years until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate by RECIST version 1.1 by independent central review. Secondary end points were duration of response, progression-free survival (PFS), overall survival, safety, and tolerability.ResultsA total of 124 patients with MSI-H/dMMR CRC (61 in cohort A, 63 in cohort B) enrolled. At data cutoff, median follow-up was 31.3 months (range, 0.2-35.6 months) for cohort A and 24.2 months (range, 0.1-27.1 months) for cohort B. Objective response rate was 33% (95% CI, 21% to 46%) and 33% (95% CI, 22% to 46%), respectively, with median duration of response not reached in either cohort. Median PFS was 2.3 months (95% CI, 2.1 to 8.1 months) and 4.1 months (95% CI, 2.1 to 18.9 months). Median overall survival was 31.4 months (95% CI, 21.4 months to not reached) and not reached (95% CI, 19.2 months to not reached). Treatment-related grade 3-4 adverse events occurred in 10 patients (16%) in cohort A and 8 (13%) in cohort B, with the most common occurring in ≥ 2 patients being pancreatitis, fatigue, increased alanine aminotransferase, and increased lipase (2 patients each; 3%) in cohort A.ConclusionPembrolizumab is effective with a manageable safety profile in patients with MSI-H/dMMR CRC.

Dataset Information

An Exceptional Response to Dostarlimab in Mismatch Repair Deficient, Microsatellite Instability-High and Platinum Refractory Endometrial Cancer.

Publications

An Exceptional Response to Dostarlimab in Mismatch Repair Deficient, Microsatellite Instability-High and Platinum Refractory Endometrial Cancer.

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