Non-small cell lung cancer, BRAF-mutated

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	Eric K. Singhi, MD MD Anderson Cancer Center Houston, TX, USA LinkedIn		Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN, USA LinkedIn

Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.

3 regimens on this page 3 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO

• 2022: Singh et al. Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline PubMed

ESMO

• 2023: Hendriks et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed

NCCN

• NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Non-Small Cell Lung Cancer.

Advanced or metastatic disease, first-line

Dabrafenib & Trametinib

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence
Planchard et al. 2017 (BRF113928 untreated)	2014-2015	Phase 2 (RT)

Biomarker eligibility criteria

• Biomarker: BRAF V600E

Targeted therapy

• Dabrafenib (Tafinlar) 150 mg PO twice per day
• Trametinib (Mekinist) 2 mg PO once per day

Continued indefinitely

References

1. BRF113928 untreated: Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland Å, Giannone V, D'Amelio AM Jr, Zhang P, Mookerjee B, Johnson BE. Dabrafenib plus trametinib in patients with previously untreated BRAF(V600E)-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017 Oct;18(10):1307-1316. Epub 2017 Sep 11. link to original article PubMed NCT01336634
   1. Update: Planchard D, Besse B, Groen HJM, Hashemi SMS, Mazieres J, Kim TM, Quoix E, Souquet PJ, Barlesi F, Baik C, Villaruz LC, Kelly RJ, Zhang S, Tan M, Gasal E, Santarpia L, Johnson BE. Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis. J Thorac Oncol. 2022 Jan;17(1):103-115. Epub 2021 Aug 26. link to original article PubMed

Advanced or metastatic disease, previously treated, BRAF inhibitor-naive

Binimetinib & Encorafenib

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence
Riely et al. 2023 (PHAROS)	2019-06-04 to 2022-06-02	Phase 2 (RT)

Biomarker eligibility criteria

• Biomarker: BRAF V600E

Targeted therapy

• Binimetinib (Mektovi) 45 mg PO twice per day on days 1 to 28
• Encorafenib (Braftovi) 450 mg PO once per day on days 1 to 28

28-day cycles

References

1. PHAROS: Riely GJ, Smit EF, Ahn MJ, Felip E, Ramalingam SS, Tsao A, Johnson M, Gelsomino F, Esper R, Nadal E, Offin M, Provencio M, Clarke J, Hussain M, Otterson GA, Dagogo-Jack I, Goldman JW, Morgensztern D, Alcasid A, Usari T, Wissel P, Wilner K, Pathan N, Tonkovyd S, Johnson BE. Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. J Clin Oncol. 2023 Jul 20;41(21):3700-3711. Epub 2023 Jun 4. Erratum in: J Clin Oncol. 2023 Dec 5;:JCO2302518. link to original article contains dosing details in manuscript PubMed NCT03915951

Dabrafenib & Trametinib

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence
Planchard et al. 2016 (BRF113928 previously treated)	2013-2015	Phase 2 (RT)

Prior treatment criteria

• 1 to 3 prior regimens, with progression

Biomarker eligibility criteria

• Biomarker: BRAF V600E

Targeted therapy

• Dabrafenib (Tafinlar) 150 mg PO twice per day
• Trametinib (Mekinist) 2 mg PO once per day

Continued indefinitely

References

1. BRF113928 previously treated: Planchard D, Besse B, Groen HJ, Souquet PJ, Quoix E, Baik CS, Barlesi F, Kim TM, Mazieres J, Novello S, Rigas JR, Upalawanna A, D'Amelio AM Jr, Zhang P, Mookerjee B, Johnson BE. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016 Jul;17(7):984-93. Epub 2016 Jun 6. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01336634
   1. Update: Planchard D, Besse B, Groen HJM, Hashemi SMS, Mazieres J, Kim TM, Quoix E, Souquet PJ, Barlesi F, Baik C, Villaruz LC, Kelly RJ, Zhang S, Tan M, Gasal E, Santarpia L, Johnson BE. Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis. J Thorac Oncol. 2022 Jan;17(1):103-115. Epub 2021 Aug 26. link to original article PubMed