Malignant solid neoplasm, NTRK-mutated
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2 regimens on this page
3 variants on this page
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Guidelines
JSCO/ESMO/ASCO/JSMO/TOS
- 2020: Yoshino et al. JSCO—ESMO—ASCO—JSMO—TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions
All lines of therapy
Entrectinib monotherapy
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Regimen
| FDA-recommended dose |
| Study | Years of enrollment | Evidence |
|---|---|---|
| Drilon et al. 2017 (ALKA-372-001) | 2012-2016 | Phase I |
| Drilon et al. 2017 (STARTRK-1) | 2012-2016 | Phase I (RT) |
Note: this is the MTD used in the phase 2 portion; it is also the FDA-recommended dose for adults.
Targeted therapy
- Entrectinib (Rozlytrek) 600 mg PO once per day
Continued indefinitely
References
- Phase 1: Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017 Apr;7(4):400-409. Epub 2017 Feb 9. link to original article link to PMC article PubMed NCT02097810; EudraCT 2012-000148-88
- Update: Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD; trial investigators. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):271-282. doi: 10.1016/S1470-2045(19)30691-6. Epub 2019 Dec 11. Erratum in: Lancet Oncol. 2020 Feb;21(2):e70. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. Erratum in: Lancet Oncol. 2020 Aug;21(8):e372. link to original article link to PMC article PubMed
Larotrectinib monotherapy
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Regimen
| FDA-recommended dose |
| Study | Years of enrollment | Evidence |
|---|---|---|
| Drilon et al. 2018 (LOXO-TRK-14001) | 2015-2017 | Phase 1 (RT) |
| Drilon et al. 2018 (SCOUT) | 2015-2017 | Phase I/II (RT) |
| Drilon et al. 2018 (NAVIGATE) | 2015-2017 | Phase II (RT) |
Note: these three trials are all reported in a single publication; the doses here are the FDA-recommended doses.
Targeted therapy
- Larotrectinib (Vitrakvi) as follows:
- Adults: 100 mg PO twice per day
- Pediatrics: 100 mg/m2 (maximum dose of 100 mg) PO twice per day
Continued indefinitely
References
- SCOUT; NAVIGATE: Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, Nathenson M, Doebele RC, Farago AF, Pappo AS, Turpin B, Dowlati A, Brose MS, Mascarenhas L, Federman N, Berlin J, El-Deiry WS, Baik C, Deeken J, Boni V, Nagasubramanian R, Taylor M, Rudzinski ER, Meric-Bernstam F, Sohal DPS, Ma PC, Raez LE, Hechtman JF, Benayed R, Ladanyi M, Tuch BB, Ebata K, Cruickshank S, Ku NC, Cox MC, Hawkins DS, Hong DS, Hyman DM. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018 Feb 22;378(8):731-739. link to original article contains protocol link to PMC article PubMed NCT02122913; NCT02637687; NCT02576431