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Management of Side Effects After Dabrafenib-trametinib Combination Therapy in Metastatic BRAF Mutant Melanoma: Two Case Reports with a Brief Literature Review

Year 2020, Volume: 42 Issue: 5, 588 - 595, 15.09.2020
https://doi.org/10.20515/otd.690957

Abstract

Malignant melanoma is an aggressive cancer type resistant to standart chemotherapy regimens in the metastatic stage. A new era has begun in the treatment of metastatic melanoma with BRAF-MEK inhibitors, which were used after the discovery of the MAP kinase signal pathway in the development of melanoma. However during the use of these drugs, a number of side effects can be observed, resulting with dose reduction and interruption or discontinuation. Drug-related side effects require a quick approach and management so that patients can benefit optimally from treatment. In this report, two patients with metastatic melanoma were evaluated, of whom one of them with pyrexia, pneumonitis noduler erythematous eruption and the other with neutropenia/ leukopenia and pyrexia due to BRAF-MEK inhibitors and clinical management of these side effects were reviewed.

References

  • Culos KA, Cuellar S. Novel targets in the treatment of advanced melanoma: new first-line treatment options. Ann Pharmacother. 2013;47(4):519-26.
  • Wellbrock C, Hurlstone A. BRAF as therapeutic target in melanoma. Biochem Pharmacol. 2010;80(5):561-7.
  • Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29(10):1239-46.
  • Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358-65.
  • Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-16.
  • Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107-14.
  • Mullard A. 2011 FDA drug approvals. Nature Publishing Group; Drugs. 2012.
  • Ballantyne AD, Garnock-Jones KP. Dabrafenib: first global approval. Drugs. 2013;73(12):1367-76.
  • Rizos H, Menzies AM, Pupo GM, et al. BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res. 2014;20(7):1965-77.
  • Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386(9992):444-51.
  • Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877-88.
  • Robert C, Karaszewska B, Schachter J, et al. Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib. N Engl J Med. 2015;372(1):30-9.
  • Robert C, Karaszewska B, Schachter J, et al. Two year estimate of overall survival in COMBI-v, a randomized, open-label, phase III study comparing the combination of dabrafenib (D) and trametinib (T) with vemurafenib (Vem) as first-line therapy in patients (pts) with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma. Eur J Cancer. 2015;51:S663-S4.
  • Ascierto PA, McArthur GA, Dréno B, et al. Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016;17(9):1248-60.
  • Larkin J, Ascierto PA, Dreno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867-76.
  • Dummer R, Ascierto PA, Gogas HJ, et al. Results of COLUMBUS part 2: a phase 3 trial of encorafenib (ENCO) plus binimetinib (BINI) versus ENCO in BRAF-mutant melanoma. Ann Oncol. 2017:12-3.
  • Gibney GT, Messina JL, Fedorenko IV, et al. Paradoxical oncogenesis—the long-term effects of BRAF inhibition in melanoma. Nat Rev Clin Oncol. 2013;10(7):390.
  • Daud A, Tsai K. Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma. Oncologist. 2017;22(7):823-33.
  • Welsh SJ, Corrie PG. Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol. 2015;7(2):122-36.
  • McArthur GA, Chapman PB, Robert C, et al. Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014;15(3):323-32.
  • Larkin J, Del Vecchio M, Ascierto PA, et al. Vemurafenib in patients with BRAFV600 mutated metastatic melanoma: an open-label, multicentre, safety study. Lancet Oncol. 2014;15(4):436-44.
  • Hauschild A, Grob JJ, Demidov LV, et al. An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM). J Clin Oncol. 2013.
  • Eroglu Z, Ribas A. Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy. Ther Adv Med Oncol. 2016;8(1):48-56.
  • Menzies AM, Long GV. Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma. Clin Cancer Res. 2014;20(8):2035-43.
  • Menzies AM, Ashworth MT, Swann S, et al. Characteristics of pyrexia in BRAF(V600E/K) metastatic melanoma patients treated with combined dabrafenib and trametinib in a phase I/II clinical trial. Ann Oncol. 2015;26(2):415-21.
  • Vera J, Paludo J, Kottschade L, et al. Case series of dabrafenib-trametinib-induced pyrexia successfully treated with colchicine. Support Care Cancer. 2019;27(10):3869-75.
  • Lee CI, Menzies AM, Haydu LE, et al. Features and management of pyrexia with combined dabrafenib and trametinib in metastatic melanoma. Melanoma Res. 2014;24(5):468-74.
  • Lee C, Menzies A, Haydu L, et al. Correlates of fever in patients receiving combined dabrafenib (GSK2118436) and trametinib (GSK1120212) for V600 BRAF-mutant metastatic melanoma. J Clin Oncol. 2012;8(Supplement S2):36-7.
  • Maeda T, Yoshino K, Yamashita C, et al. Dynamics of neutrophil and C-reactive protein reflect the clinical course of pyrexia during combination therapy with dabrafenib and trametinib. J Dermatol. 2019;46(8):716-9.
  • Macesic N, Ameratunga M, Grayson ML, et al. Fever in melanoma: new drugs or bugs? Clin Microbiol Infect. 2015;21(10):e77-8.
  • Clay TD, Bowyer SEJA-cd. Dabrafenib and trametinib treatment-associated fevers in metastatic melanoma causing extreme elevation in procalcitonin in the absence of infection. Anticancer Drugs. 2018;29(8):802-5.
  • Heinzerling L, Eigentler TK, Fluck M, et al. Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management. ESMO Open. 2019;4(3):e000491.
  • Schmitt L, Schumann T, Löser C, et al. Treatment. Vemurafenib-induced pulmonary injury. Onkologie. 2013;36(11):685-6.
  • Lafabregue E, Arnault JP, Auquier M, et al. Two cases of pneumonitis induced by targeted therapy. Melanoma Res. 2019;29(4):441-3.
  • Min JH, Lee HY, Lim H, et al. Drug-induced interstitial lung disease in tyrosine kinase inhibitor therapy for non-small cell lung cancer: a review on current insight. Cancer Chemother Pharmacol. 2011;68(5):1099-109.

BRAF Mutant Metastatik Melanomda Dabrafenib-trametinib Kombinasyon Tedavisi Sonrası Gelişen Yan Etki Yönetimi: İki Olgu Sunumuyla Birlikte Literatür Derlemesi

Year 2020, Volume: 42 Issue: 5, 588 - 595, 15.09.2020
https://doi.org/10.20515/otd.690957

Abstract

Malign melanom, metastatik evrede standart kemoterapi rejimlerine dirençli agresif seyirli bir kanser türüdür. MAP kinaz sinyal yolağının melanom gelişimindeki rolünün keşfinden sonra kullanılmaya başlanan BRAF-MEK inhibitörleri ile metastatik melanomun tedavisinde yeni bir döneme girilmiştir. Ancak bu ilaçların kullanımı sırasında doz redüksiyonu, ilaca ara verme ve ilaç kesilmesine kadar gidebilen bir takım yan etkiler gözlenebilir. İlaç ilişkili yan etkiler, hastaların tedaviden optimal şekilde yararlanabilmeleri için hızlı bir yaklaşım ve yönetim gerektirir. Bu olgu sunumu ve kısa derlemede, BRAF-MEK inhibitörü kombinasyonu ile birinde ilaç ateşi, pnömonit, nodüler eritematöz döküntü diğerinde ise ilaç ateşi, lökopeni, nötropeni gelişen iki metastatik melanom olgusu ve gelişen yan etkilerin yönetimine yönelik klinik yaklaşım özetlendi.

References

  • Culos KA, Cuellar S. Novel targets in the treatment of advanced melanoma: new first-line treatment options. Ann Pharmacother. 2013;47(4):519-26.
  • Wellbrock C, Hurlstone A. BRAF as therapeutic target in melanoma. Biochem Pharmacol. 2010;80(5):561-7.
  • Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29(10):1239-46.
  • Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358-65.
  • Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-16.
  • Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107-14.
  • Mullard A. 2011 FDA drug approvals. Nature Publishing Group; Drugs. 2012.
  • Ballantyne AD, Garnock-Jones KP. Dabrafenib: first global approval. Drugs. 2013;73(12):1367-76.
  • Rizos H, Menzies AM, Pupo GM, et al. BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res. 2014;20(7):1965-77.
  • Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386(9992):444-51.
  • Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877-88.
  • Robert C, Karaszewska B, Schachter J, et al. Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib. N Engl J Med. 2015;372(1):30-9.
  • Robert C, Karaszewska B, Schachter J, et al. Two year estimate of overall survival in COMBI-v, a randomized, open-label, phase III study comparing the combination of dabrafenib (D) and trametinib (T) with vemurafenib (Vem) as first-line therapy in patients (pts) with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma. Eur J Cancer. 2015;51:S663-S4.
  • Ascierto PA, McArthur GA, Dréno B, et al. Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016;17(9):1248-60.
  • Larkin J, Ascierto PA, Dreno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867-76.
  • Dummer R, Ascierto PA, Gogas HJ, et al. Results of COLUMBUS part 2: a phase 3 trial of encorafenib (ENCO) plus binimetinib (BINI) versus ENCO in BRAF-mutant melanoma. Ann Oncol. 2017:12-3.
  • Gibney GT, Messina JL, Fedorenko IV, et al. Paradoxical oncogenesis—the long-term effects of BRAF inhibition in melanoma. Nat Rev Clin Oncol. 2013;10(7):390.
  • Daud A, Tsai K. Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma. Oncologist. 2017;22(7):823-33.
  • Welsh SJ, Corrie PG. Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol. 2015;7(2):122-36.
  • McArthur GA, Chapman PB, Robert C, et al. Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014;15(3):323-32.
  • Larkin J, Del Vecchio M, Ascierto PA, et al. Vemurafenib in patients with BRAFV600 mutated metastatic melanoma: an open-label, multicentre, safety study. Lancet Oncol. 2014;15(4):436-44.
  • Hauschild A, Grob JJ, Demidov LV, et al. An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM). J Clin Oncol. 2013.
  • Eroglu Z, Ribas A. Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy. Ther Adv Med Oncol. 2016;8(1):48-56.
  • Menzies AM, Long GV. Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma. Clin Cancer Res. 2014;20(8):2035-43.
  • Menzies AM, Ashworth MT, Swann S, et al. Characteristics of pyrexia in BRAF(V600E/K) metastatic melanoma patients treated with combined dabrafenib and trametinib in a phase I/II clinical trial. Ann Oncol. 2015;26(2):415-21.
  • Vera J, Paludo J, Kottschade L, et al. Case series of dabrafenib-trametinib-induced pyrexia successfully treated with colchicine. Support Care Cancer. 2019;27(10):3869-75.
  • Lee CI, Menzies AM, Haydu LE, et al. Features and management of pyrexia with combined dabrafenib and trametinib in metastatic melanoma. Melanoma Res. 2014;24(5):468-74.
  • Lee C, Menzies A, Haydu L, et al. Correlates of fever in patients receiving combined dabrafenib (GSK2118436) and trametinib (GSK1120212) for V600 BRAF-mutant metastatic melanoma. J Clin Oncol. 2012;8(Supplement S2):36-7.
  • Maeda T, Yoshino K, Yamashita C, et al. Dynamics of neutrophil and C-reactive protein reflect the clinical course of pyrexia during combination therapy with dabrafenib and trametinib. J Dermatol. 2019;46(8):716-9.
  • Macesic N, Ameratunga M, Grayson ML, et al. Fever in melanoma: new drugs or bugs? Clin Microbiol Infect. 2015;21(10):e77-8.
  • Clay TD, Bowyer SEJA-cd. Dabrafenib and trametinib treatment-associated fevers in metastatic melanoma causing extreme elevation in procalcitonin in the absence of infection. Anticancer Drugs. 2018;29(8):802-5.
  • Heinzerling L, Eigentler TK, Fluck M, et al. Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management. ESMO Open. 2019;4(3):e000491.
  • Schmitt L, Schumann T, Löser C, et al. Treatment. Vemurafenib-induced pulmonary injury. Onkologie. 2013;36(11):685-6.
  • Lafabregue E, Arnault JP, Auquier M, et al. Two cases of pneumonitis induced by targeted therapy. Melanoma Res. 2019;29(4):441-3.
  • Min JH, Lee HY, Lim H, et al. Drug-induced interstitial lung disease in tyrosine kinase inhibitor therapy for non-small cell lung cancer: a review on current insight. Cancer Chemother Pharmacol. 2011;68(5):1099-109.
There are 35 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section DERLEME
Authors

Yasemin Sağdıç Karateke 0000-0002-3287-6248

Lütfiye Demir 0000-0003-0492-3454

Publication Date September 15, 2020
Published in Issue Year 2020 Volume: 42 Issue: 5

Cite

Vancouver Sağdıç Karateke Y, Demir L. BRAF Mutant Metastatik Melanomda Dabrafenib-trametinib Kombinasyon Tedavisi Sonrası Gelişen Yan Etki Yönetimi: İki Olgu Sunumuyla Birlikte Literatür Derlemesi. Osmangazi Tıp Dergisi. 2020;42(5):588-95.


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