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Gynecol Oncol. 2019 Feb 18. pii: S0090-8258(19)30108-8. doi: 10.1016/j.ygyno.2019.02.005. [Epub ahead of print]

Impact of somatic molecular profiling on clinical trial outcomes in rare epithelial gynecologic cancer patients.

Author information

1
Department of Medicine, Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
2
Department of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
3
Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
4
Department of Medicine, Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Cancer Genomics Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
5
Department of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
6
Department of Medicine, Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address: Amit.Oza@uhn.ca.

Abstract

OBJECTIVES:

Conducting clinical trials in rare malignancies is challenging due to the limited number of patients and differences in biologic behavior. We investigated the feasibility and clinical utility of using genomic profiling for rare gynecologic malignancies.

METHODS:

Rare epithelial gynecologic cancer patients were analyzed for somatic variants through an institutional molecular profiling program using the Sequenom MassArray platform or the TruSeq Amplicon Cancer Panel on the MiSeq platform. Clinical trial outcomes by RECIST 1.1, and time on treatment were evaluated.

RESULTS:

From March 2012 to November 2015, 767 gynecologic patients were enrolled and 194 (27%) were classified as rare epithelial malignancies. At least one somatic mutation was identified in 72% of patients, most commonly in TP53 (39%), KRAS (28%) and PIK3CA (27%). A total of 14% of patients were treated on genotype-matched trials. There were no significant differences in overall response rate between genotype-matched versus unmatched trials, nor in median time on treatment between genotype trials and the immediate prior systemic standard treatment. Among 13 evaluable Low Grade Serous ovarian cancer patients treated on genotype-matched trials with MEK inhibitor-based targeted combinations, there were four partial responses.

CONCLUSIONS:

Somatic molecular profiling is feasible and enables the identification of patients with rare gynecologic cancers who are candidates for genotype-matched clinical trials. Genotype-matched trials, predominantly MEK-based combinations in KRAS and/or NRAS mutant Low Grade Serous ovarian cancer patients, and genotype-unmatched trials, have shown potential clinical activity. Prospective trials with integrated genotyping are warranted to assess the clinical utility of next generation sequencing tests as a standard clinical application in rare malignancies.

KEYWORDS:

Low Grade Serous ovarian cancer; Molecular profiling; Rare gynecologic malignancies; Targeted therapies

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