Difference between revisions of "Non-small cell lung cancer, ROS1-positive"
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*[[Ceritinib (Zykadia)]] 750 mg PO once per day on an empty stomach | *[[Ceritinib (Zykadia)]] 750 mg PO once per day on an empty stomach | ||
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''Note: this was an expansion cohort of a phase I study.'' | ''Note: this was an expansion cohort of a phase I study.'' | ||
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*[[Crizotinib (Xalkori)]] 250 mg PO twice per day | *[[Crizotinib (Xalkori)]] 250 mg PO twice per day | ||
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''Note: this is the FDA-recommended dosing for "moderate" hepatic impairment.'' | ''Note: this is the FDA-recommended dosing for "moderate" hepatic impairment.'' | ||
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*[[Crizotinib (Xalkori)]] 200 mg PO twice per day | *[[Crizotinib (Xalkori)]] 200 mg PO twice per day | ||
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''Note: this is the FDA-recommended dosing for "severe" hepatic or renal impairment.'' | ''Note: this is the FDA-recommended dosing for "severe" hepatic or renal impairment.'' | ||
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*[[Crizotinib (Xalkori)]] 250 mg PO once per day | *[[Crizotinib (Xalkori)]] 250 mg PO once per day | ||
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''Note: this is the MTD used in the phase 2 portion; it is also the FDA-recommended dose for adults.'' | ''Note: this is the MTD used in the phase 2 portion; it is also the FDA-recommended dose for adults.'' | ||
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*[[Entrectinib (Rozlytrek)]] 600 mg PO once per day | *[[Entrectinib (Rozlytrek)]] 600 mg PO once per day | ||
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*[[Lorlatinib (Lorbrena)]] 100 mg PO once per day | *[[Lorlatinib (Lorbrena)]] 100 mg PO once per day | ||
Revision as of 01:46, 30 July 2020
| Page editor | Section editor | ||
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Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN  AmitKulkarniMD
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Travis Osterman, DO, MS Vanderbilt University Nashville, TN TravisOsterman |
Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.
6 regimens on this page
8 variants on this page
|
Advanced or metastatic disease, ROS1 inhibitor-naive
Ceritinib monotherapy
| back to top |
Regimen
| Study | Evidence | Efficacy |
|---|---|---|
| Lim et al. 2017 | Phase II | ORR: 67% (95% CI, 48-81) |
Targeted therapy
- Ceritinib (Zykadia) 750 mg PO once per day on an empty stomach
28-day cycles
References
- Lim SM, Kim HR, Lee JS, Lee KH, Lee YG, Min YJ, Cho EK, Lee SS, Kim BS, Choi MY, Shim HS, Chung JH, La Choi Y, Lee MJ, Kim M, Kim JH, Ali SM, Ahn MJ, Cho BC. Open-label, multicenter, phase II study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement. J Clin Oncol. 2017 Aug 10;35(23):2613-2618. Epub 2017 May 18. link to original article contains verified protocol PubMed
Crizotinib monotherapy
| back to top |
Regimen variant #1, standard-dose
| FDA-recommended dose |
| Study | Years of enrollment | Evidence | Efficacy |
|---|---|---|---|
| Shaw et al. 2014 (PROFILE 1001) | 2010-2013 | Non-randomized (RT) | ORR: 72% (95% CI, 58-84) |
Note: this was an expansion cohort of a phase I study.
Targeted therapy
- Crizotinib (Xalkori) 250 mg PO twice per day
28-day cycles
Regimen variant #2, 200 mg twice per day
| FDA-recommended dose |
Note: this is the FDA-recommended dosing for "moderate" hepatic impairment.
Targeted therapy
- Crizotinib (Xalkori) 200 mg PO twice per day
Continued indefinitely
Regimen variant #3, 250 mg/day
| FDA-recommended dose |
Note: this is the FDA-recommended dosing for "severe" hepatic or renal impairment.
Targeted therapy
- Crizotinib (Xalkori) 250 mg PO once per day
Continued indefinitely
References
- PROFILE 1001: Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71. Epub 2014 Sep 27. link to original article link to PMC article contains verified protocol PubMed
Entrectinib monotherapy
| back to top |
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
Advanced or metastatic disease, ROS1 inhibitor-exposed
Lorlatinib monotherapy
| back to top |
Regimen
| Study | Evidence |
|---|---|
| Shaw et al. 2017 (B7461001) | Phase I, <20 pts in this subgroup |
Targeted therapy
- Lorlatinib (Lorbrena) 100 mg PO once per day
Continued indefinitely
References
- Phase 1: Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. Epub 2017 Oct 23. link to original article contains protocol PubMed
Additional resources
Investigational agents
Drugs with some degree of promising activity in clinical trials.