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Alexander Drilon, MD

Gregory J. Riely, MD, PhD


Rare Case of TPM3-NTRK Rearrangement in Recurrent Ovarian Cancer

By: Lauren Harrison, MS
Posted: Friday, March 25, 2022

A group in Japan published a case report in Molecular and Clinical Oncology describing a rare case of recurrent ovarian cancer with a TPM3-NTRK1 gene fusion where the TRK inhibitor entrectinib was not effective. Although the NTRK gene fusion was detected by next-generation sequencing, immunohistochemistry was negative for TRK, suggesting that confirmation of TRK expression may be needed prior to entrectinib administration, according to Keiya Fujimori, MD, PhD, of Fukushima Medical University School of Medicine, Japan, and colleagues.

This case describes a 56-year-old woman who presented with bilateral ovarian tumors with multiple disseminations into the peritoneum, bilateral pleural effusions, and congestion of the pelvic and para-aortic lymph nodes. The patient was diagnosed with stage IV ovarian cancer and was treated with neoadjuvant paclitaxel and carboplatin. She underwent interval debulking surgery, followed by three more courses of chemotherapy. About 10 months later, she presented with multiple metastases around the liver and was given a third course of chemotherapy along with partial hepatectomy. She then had two more recurrences of disease, and no chemotherapeutic regimens were effective.

The patient underwent next-generation sequencing because there were no more standard therapies available. Sequencing revealed a missense variant of TP53 and a TPM3-NTRK1 rearrangement, and the patient was subsequently started on entrectinib. After 6 weeks of therapy, the patient’s tumor markers were increased, and imaging revealed progression of metastasis. Entrectinib was discontinued, and the patient died 1 month later. After the patient’s death, immunohistochemical staining of primary and recurrent sites revealed no evidence of any NTRK fusion.

The authors proposed that this patient’s lack of response to entrectinib was because the TRK protein was not expressed. They suggested that immunohistochemistry may be necessary to predict response to entrectinib in patients where NTRK fusions are seen on sequencing.

Disclosure: The study authors reported no conflicts of interest.

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