Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients

Hecht, Markus; Zimmer, Lisa; Loquai, Carmen; Weishaupt, Carsten; Gutzmer, Ralf; Schuster, Barbara; Gleisner, S.; Schulze, B.; Goldinger, Simone M.; Berking, Carola; Forschner, Andrea; Clemens, Patrick; Grabenbauer, Gerhard G.; Müller-Brenne, Tina; Bauch, Julia; Eich, H.T.; Grabbe, Stephan; Schadendorf, Dirk; Schuler, Gerold; Keikavoussi, Petra; Semrau, Sabine; Fietkau, Rainer; Distel, Luitpold; Heinzerling, Lucie

doi:10.1093/annonc/mdv139

Cited by 113 publications

(103 citation statements)

References 27 publications

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“…30 In a nonrandomized comparison with patients receiving vemurafenib, vemurafenib was associated with significantly higher levels of acute radiodermatitis than dabrafenib (40% vs 26%, P = 0.07). There was no radiodermatitis > grade 1 seen with SRS.…”

Section: Radiotherapymentioning

confidence: 91%

Optimizing combination dabrafenib and trametinib therapy in BRAF mutation‐positive advanced melanoma patients: Guidelines from Australian melanoma medical oncologists

Atkinson

Long

Menzies

et al. 2016

Asia-Pac J Clncl Oncology

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BRAF mutations occur commonly in metastatic melanomas and inhibition of mutant BRAF and the downstream kinase MEK results in rapid tumor regression and prolonged survival in patients. Combined therapy with BRAF and MEK inhibition improves response rate, progression free survival and overall survival compared with single agent BRAF inhibition, and reduces the skin toxicity that is seen with BRAF inhibitor monotherapy. However, this combination is associated with an increase in other toxicities, particularly drug-related pyrexia, which affects approximately 50% of patients treated with dabrafenib and trametinib (CombiDT). We provide guidance on managing adverse events likely to arise during treatment with combination BRAF and MEK inhibition with CombiDT: pyrexia, skin conditions, fatigue; and discuss management of CombiDT during surgery and radiotherapy. By improving tolerability and in particular preventing unnecessary treatment cessations or reduction in drug exposure, best outcomes can be achieved for patients undergoing CombiDT therapy.

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Section: Radiotherapymentioning

confidence: 91%

Optimizing combination dabrafenib and trametinib therapy in BRAF mutation‐positive advanced melanoma patients: Guidelines from Australian melanoma medical oncologists

Atkinson

Long

Menzies

et al. 2016

Asia-Pac J Clncl Oncology

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“…The development of BRAF inhibitors (i.e., vemurafenib, dabrafenib) has led to a significant improvement in the overall survival among patients who harbor this mutation (125,130,131). Interestingly, BRAF inhibitor was found to have radio sensitization effect (132,133). However, the radiosensitization effect of BRAF inhibitor also increased the risk of skin toxicities with radiation (133)(134)(135)(136).…”

Section: Rt With Concomitant Agentsmentioning

confidence: 99%

“…Interestingly, BRAF inhibitor was found to have radio sensitization effect (132,133). However, the radiosensitization effect of BRAF inhibitor also increased the risk of skin toxicities with radiation (133)(134)(135)(136). Due to the minimum skin dose from SRS, several studies that evaluated BRAF inhibitor with SRS for patients with brain metastases reported favorable outcome (137)(138)(139).…”

Section: Rt With Concomitant Agentsmentioning

confidence: 99%

Radiation Therapy for Melanoma

Shi

2017

Cutaneous Melanoma: Etiology and Therapy

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Although melanoma is a relative radioresistant tumor, radiation therapy (RT) remains a valid and effective treatment option for the management of melanoma. RT as a primary treatment is often offered in well-defined situations, such as medical inoperability, lentiginous melanoma, mucosal melanoma, and ocular melanoma. Adjuvant RT following lymphadenectomy in node-positive melanoma patients prevents local and regional recurrence; however, the role of adjuvant RT remains controversial and underutilized due to lack of overall survival benefit. On the other hand, RT is highly effective in providing symptom palliation for metastatic melanoma and is widely used. Advanced RT technologies such as stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) can achieve excellent local control with minimum toxicities. They are commonly used in the management of brain, lung, spine, and liver metastases. Most recently, it is under active investigation on combining RT with new systemic options, such as targeted therapy, or immunotherapy. The advancements in the treatment of patients with melanoma highlight the importance of multidisciplinary management in this disease. Radiation therapy will continue to be one of the key therapeutic options.

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“…Vemurafenib kezelés mellett gyakran észlelünk fotoszenzitivitást. Sugárkezelt bőrterület vagy belső szerv súlyos akut gyulladásos reakciója jelentkezhet a gyógyszerszedés alatt az irradiációval egyidejűleg vagy röviddel utána (radioszenzitizáció), de akár jóval később (átlag 1 hónappal) a sugárkezelés befejezése után ("radiation recall") (21,22). A BRAF inhibitorok specifikus mellékhatásaként benignus (pl.…”

Section: Braf Inhibitor Kezelés (Hatékonyság Mellékhatás)unclassified

Targeted therapy for BRAF-mutation positive metastatic melanoma

Szabó¹,

Ócsai²,

Kiss³

et al. 2017

BVSZ

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ÖSSZEFOGLALÁS A BRAFV600E/K génmutáció a melanoma kialakulásá-ban és progressziójában is fontos pathogenetikai tényező. Az esetek felében kimutatható a tumor metasztázisban és hatásának ellensúlyozására kifejlesztett célzott molekulá- Kulcsszavak: áttétes melanoma -BRAF inhibitor -MEK inhibitor -gyógyszer mellékhatás SUMMARY An important pathogenic factor in both the development and progression of melanoma is the V600E/K mutation of BRAF, which can be found in half of metastatic tumors. It is unsurprising therefore that molecular inhibitors targeting its effect are able to offer significantly higher progression free and overall survival as compared to conventional chemotherapy in the majority of patients diagnosed with metastatic melanoma. Moreover, the combination of BRAF-and MEK inhibitor therapy has greatly improved the prognosis of patients with confirmed mutations in distant metastases, showing that optimal use of new therapeutic agents by broadening clinical expertise is an effective way of expanding the inventory of anti-melanoma agents. The management of potential adverse events related to new treatments is also improved by their widespread use and the consequent enhancement of practical knowledge related to the new agents, ultimately leading to the improvement of quality of life of patients. Key words: metastatic melanoma -BRAF inhibitor -MEK inhibitor -drug adverse eventA melanoma pathofiziológiájáról szerzett, az elmúlt év-tizedben robbanásszerűen felhalmozódott ismereteink és a modern biotechnológia lehetővé tették új típusú onkoterá-piák megjelenését, mint amilyenek a célzott molekuláris inhibitorok vagy a biológiai terápiák, és ezzel megváltoztatták a metasztatikus betegek túlélési esélyeit és átírták a korábbi kezelési irányvonalakat (1-3). A melanoma kialakulásában és progressziójában kulcsszerepet játszó génmutációk komplex módon, az intracelluláris jelátviteli folyamatok kö-zötti egyensúly megbomlását okozva vezetnek megnöve-kedett sejttúléléséhez, kórosan fokozott sejtproliferációhoz. Az egyik legfontosabb pathogenetikai lépés a MAPK (Mitogén Aktivált Protein-Kináz)-útvonal aktivitásának fokozódása (4), ami igen gyakran, a melanomás eseteknek a 160 Levelező szerző: Dr. Szabó Imre Lőrinc

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Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients

Abstract: Radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib.

Cited by 113 publications

References 27 publications

Optimizing combination dabrafenib and trametinib therapy in BRAF mutation‐positive advanced melanoma patients: Guidelines from Australian melanoma medical oncologists

Optimizing combination dabrafenib and trametinib therapy in BRAF mutation‐positive advanced melanoma patients: Guidelines from Australian melanoma medical oncologists

Radiation Therapy for Melanoma

Targeted therapy for BRAF-mutation positive metastatic melanoma

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