PMID- 34458597 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220426 IS - 2405-6308 (Electronic) IS - 2405-6308 (Linking) VI - 30 DP - 2021 Sep TI - Phase I/II trial of concurrent extracranial palliative radiation therapy with Dabrafenib and Trametinib in metastatic BRAF V600E/K mutation-positive cutaneous Melanoma. PG - 95-99 LID - 10.1016/j.ctro.2021.08.006 [doi] AB - 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. CI - (c) 2021 The Author(s). FAU - Wang, Wei AU - Wang W AD - Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW 2145, Australia. AD - Sydney Medical School, The University of Sydney, Camperdown, NSW 2006, Australia. FAU - Smith, Jessica Louise AU - Smith JL AD - Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW 2145, Australia. FAU - Carlino, Matteo Salvatore AU - Carlino MS AD - Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW 2145, Australia. AD - Sydney Medical School, The University of Sydney, Camperdown, NSW 2006, Australia. FAU - Burmeister, Bryan AU - Burmeister B AD - GenesisCare, Fraser Coast, QLD 4655, Australia. FAU - Pinkham, Mark Blayne AU - Pinkham MB AD - Department Radiation Oncology, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia. AD - Queensland University of Technology, Brisbane City, QLD 4000, Australia. FAU - Fogarty, Gerald Blaise AU - Fogarty GB AD - Mater Genesis Care Radiotherapy Centre, 25 Rocklands RD, Crows Nest, NSW 2065, Australia. FAU - Christie, David Robert Harry AU - Christie DRH AD - Genesiscare, Tugun, QLD 4224, Australia. AD - Bond University, Robina, QLD 4226, Australia. FAU - Estall, Vanessa AU - Estall V AD - Liverpool Cancer Therapy Centre, Liverpool, NSW 2170, Australia. FAU - Shackleton, Mark AU - Shackleton M AD - Department of Oncology, Alfred Health, Melbourne, VIC 3004, Australia. AD - Central Clinical School, Monash University, Melbourne, VIC 3004, Australia. FAU - Clements, Arthur AU - Clements A AD - SAN Integrated Cancer Centre, Wahroonga, NSW 2076, Australia. FAU - Wolfe, Rory AU - Wolfe R AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia. FAU - Thao, Le Thi Phuong AU - Thao LTP AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia. FAU - Paton, Elizabeth Jane AU - Paton EJ AD - Melanoma and Skin Cancer Trials, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia. FAU - Steel, Victoria AU - Steel V AD - Melanoma and Skin Cancer Trials, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia. FAU - Williams, Narelle Catherine AU - Williams NC AD - Melanoma and Skin Cancer Trials, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia. LA - eng PT - Journal Article DEP - 20210814 PL - Ireland TA - Clin Transl Radiat Oncol JT - Clinical and translational radiation oncology JID - 101713416 PMC - PMC8379352 OTO - NOTNLM OT - BRAF inhibitors OT - Dabrafenib OT - MEK inhibitors OT - Melanoma OT - Radiation therapy OT - Skin toxicity OT - Trametinib COIS- The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [GlaxoSmithKline and Novartis provided initial seed funding for this clinical trial. GlaxoSmithKline or Novartis had no involvement in the data analysis and preparation of this manuscript.] EDAT- 2021/08/31 06:00 MHDA- 2021/08/31 06:01 PMCR- 2021/08/14 CRDT- 2021/08/30 06:05 PHST- 2021/06/08 00:00 [received] PHST- 2021/08/03 00:00 [revised] PHST- 2021/08/05 00:00 [accepted] PHST- 2021/08/30 06:05 [entrez] PHST- 2021/08/31 06:00 [pubmed] PHST- 2021/08/31 06:01 [medline] PHST- 2021/08/14 00:00 [pmc-release] AID - S2405-6308(21)00074-4 [pii] AID - 10.1016/j.ctro.2021.08.006 [doi] PST - epublish SO - Clin Transl Radiat Oncol. 2021 Aug 14;30:95-99. doi: 10.1016/j.ctro.2021.08.006. eCollection 2021 Sep.