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Larotrectinib ORR — SCE Medical Oncology MCQ

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HardGI CancersLarotrectinib ORRSCE Medical Oncology

Comprehensive profiling in a treatment-refractory colorectal cancer reports an unexpected NTRK3 fusion at low read support. Which interpretation is most appropriate before considering a TRK inhibitor?

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Correct answer: E — A validated expressed fusion predicts substantial sensitivity, subject to current UK access

An orthogonally confirmed, expressed in-frame NTRK fusion predicts strong TRK-inhibitor sensitivity, subject to current UK access arrangements. A validated genomic NTRK3 rearrangement predicts sensitivity with unconfirmed transcript expression: an unexpected low-read genomic call should be shown to create an expressed functional fusion. A validated NTRK3 copy-number gain predicts substantial sensitivity to TRK inhibition: copy gain is not equivalent to an oncogenic fusion. A validated NTRK3 point mutation predicts substantial sensitivity to TRK inhibition: most NTRK point variants are not established tumour-agnostic drivers. A validated NTRK3 fusion predicts sensitivity with access assessed after treatment selection: biological actionability and commissioned access are separate requirements.

Reference: ESMO recommendations on standard methods to detect NTRK fusions (Published September 2019): https://pubmed.ncbi.nlm.nih.gov/31268127/; Larotrectinib in TRK-fusion-positive cancers in adults and children (Published February 2018): https://pubmed.ncbi.nlm.nih.gov/29466156/; NICE TA630 larotrectinib for NTRK-fusion-positive solid tumours (Published May 2020; current NICE TA): https://www.nice.org.uk/guidance/ta630/chapter/1-Recommendations