Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion Journal Article
| Authors: | O'Reilly, E. M.; Hechtman, J. F. |
| Article Title: | Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion |
| Abstract: | BACKGROUND: Although rare, NTRK gene fusions are known to be oncogenic drivers in pancreatic ductal adenocarcinoma (PDAC). We report the response of a metastatic CTRC-NTRK1 gene fusion-positive PDAC to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib and the eventual development of resistance to treatment. PATIENT, METHODS AND RESULTS: A 61-year-old woman presented with a 2.5-cm mass in the body of the pancreas and a 1.2-cm liver lesion on routine follow-up for endometrial cancer that was in complete remission. Liver biopsy confirmed a primary PDAC unrelated to the endometrial cancer. The patient was treated with gemcitabine, nab-paclitaxel and ADI-PEG 20 for 12 months until disease progression and toxicity emerged [best overall response (BOR): partial response (PR)]. The patient switched to a modified regimen of folinic acid, fluorouracil, irinotecan and oxaliplatin for 4 months until neuropathy occurred. Oxaliplatin was withheld until disease progression 6 months later (BOR: stable disease). Despite recommencing oxaliplatin, the disease continued to progress. At this time, somatic profiling of the liver lesion revealed a CTRC-NTRK1 gene fusion. Treatment with larotrectinib 100 mg twice daily was commenced with BOR of PR at 2 months. The patient progressed after 6 months and was re-biopsied. Treatment was switched to the investigational next-generation TRK inhibitor selitrectinib (BAY 2731954, LOXO-195) 100 mg twice daily. After 2 months, the disease progressed and dabrafenibtrametinib combination therapy was initiated due to existence of a BRAF-V600E mutation. However, the cancer continued to progress and the patient died 2 months later. CONCLUSIONS: Targeted TRK inhibition with larotrectinib in PDAC harbouring a CTRC-NTRK1 gene fusion is well tolerated and can improve quality of life for the patient. However, acquired resistance to therapy can emerge in some patients. Next-generation TRK inhibitors such as selitrectinib are currently in development to overcome this resistance (NCT02576431; NCT03215511). © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. |
| Keywords: | pancreatic adenocarcinoma; larotrectinib; selitrectinib; trk fusion cancer; ntrk gene fusion; tropomyosin receptor kinase inhibition |
| Journal Title: | Annals of Oncology |
| Volume: | 30 |
| Issue: | Suppl. 8 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2019-11-01 |
| Start Page: | viii36 |
| End Page: | viii40 |
| Language: | English |
| DOI: | 10.1093/annonc/mdz385 |
| PUBMED: | 31605106 |
| PROVIDER: | scopus |
| PMCID: | PMC6859823 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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