Phase I/II trial of concurrent extracranial palliative radiation therapy with Dabrafenib and Trametinib in metastatic BRAF V600E/K mutation-positive cutaneous Melanoma

Clinical and Translational Radiation Oncology

Le Thi Phuong Thao¹  Narelle Catherine Williams²  Matteo Salvatore Carlino³  Mark Shackleton⁴  Jessica Louise Smith⁵  Gerald Blaise Fogarty⁵  Vanessa Estall⁶  Victoria Steel⁷  Bryan Burmeister⁸  Mark Blayne Pinkham⁸  Wei Wang⁸  David Robert Harry Christie⁹  Rory Wolfe^1,10  Elizabeth Jane Paton^1,11  Arthur Clements^1,12 

[1]Bond University, Robina, QLD 4226, Australia

[2]Central Clinical School, Monash University, Melbourne, VIC 3004, Australia

[3]Corresponding author at: Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW 2145, Australia.

[4]Queensland University of Technology, Brisbane City, QLD 4000, Australia

[5]Sydney Medical School, The University of Sydney, Camperdown, NSW 2006, Australia

[6]Department Radiation Oncology, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia

[7]Department of Oncology, Alfred Health, Melbourne, VIC 3004, Australia

[8]Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW 2145, Australia

[9]GenesisCare, Fraser Coast, QLD 4655, Australia

[10]Genesiscare, Tugun, QLD 4224, Australia

[11]Liverpool Cancer Therapy Centre, Liverpool, NSW 2170, Australia

[12]Mater Genesis Care Radiotherapy Centre, 25 Rocklands RD, Crows Nest, NSW 2065, Australia

关键词: Melanoma;    Radiation therapy;    BRAF inhibitors;    MEK inhibitors;    Dabrafenib;    Trametinib;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Concurrent treatment with BRAF inhibitors and palliative radiation therapy (RT) could be associated with increased toxicity, especially skin toxicity. Current Eastern Cooperative Oncology Group (ECOG) consensus guideline recommend ceasing BRAF inhibitors during RT. There is a lack of data regarding concurrent RT with combined BRAF and MEK inhibitors. This single-arm phase I/II trial was designed to assess the safety and tolerability of palliative RT with concurrent Dabrafenib and Trametinib in patients with BRAF-mutant metastatic melanoma. Materials and methods: Patients received Dabrafenib and Trametinib before and during palliative RT to soft tissue, nodal or bony metastases. The RT dose was escalated stepwise during the study period. Toxicity data including clinical photographs of the irradiated area was collected for up to 12 months following completion of RT. Results: Between June 2016 to October 2019, ten patients were enrolled before the study was stopped early due to low accrual rate. Six patients were treated at level 1 (20 Gy in 5 fractions, any location) and 4 patients at level 2a (30 Gy in 10 fractions with no abdominal viscera exposed). All alive patients completed one year of post-RT follow-up. Of the 82 adverse events (AEs) documented, the majority (90%) were grade 1 and 2. Eight grade 3 events (10%) occurred in five patients, only one was treatment-related (grade 3 fever due to Dabrafenib and Trametinib). No patients experienced grade 3 or 4 RT related toxicities, including skin toxicities. One serious AE was documented in relation to a grade 3 fever due to Dabrafenib and Trametinib requiring hospitalisation. Conclusions: The lack of grade 3 and 4 RT-related toxicities in our study suggests that Dabrafenib and Trametinib may be continued concurrently during fractionated non-visceral palliative RT to extracranial sites.

【 授权许可】

Unknown