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CC BY-NC-ND 4.0 · South Asian J Cancer 2021; 10(03): 187-189
DOI: 10.1055/s-0041-1736032
Original Article: Skin Cancer

Early Experience with Dabrafenib–Trametinib Combination in Patients with BRAF-Mutated Malignant Melanoma—A Single-Center Experience

Sandip Ganguly 
1   Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal, India
,
Joydeep Ghosh
1   Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal, India
,
Deepak Mishra
2   Department of Molecular Pathology, Tata Medical Center, Kolkata, West Bengal, India
,
Gautam Biswas
3   Department of Plastic Surgery, Tata Medical Center, Kolkata, West Bengal, India
,
Deepak Dabkara
1   Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal, India
,
Somanth Roy
1   Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal, India
,
Bivas Biswas
1   Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal, India
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Abstract

Background Combination of dabrafenib–trametinib is one of the standard treatments in patients with BRAF-mutated advanced malignant melanoma (MM). Real-world data on the usage of this combination is scarce, especially from India. Here, we are reporting our early experience with the usage of this combination therapy.

Materials and Methods This is a single institutional data assessment of patients with BRAF-mutated MM registered and treated with BRAF–MEK inhibitors in our hospital. Clinico-pathological features and treatment details were reviewed for all patients.

Results A total of seven patients with BRAF-mutated MM treated with this combination therapy with a median age of 66.5 years (range: 49–72 years) and a male:female ratio of 3:4. Six (85.7%) patients had metastatic disease at presentation. In total, 80% of our patient population had two or less than two sites of metastasis at presentation. The initial response rate of the study population was 71%. The drug was well tolerated with fever being the most common side effect which was seen in two (28.5%) of the patients.

Conclusion Combination of dabrafenib–trametinib is effective in patients with BRAF-mutated MM with good tolerability. Further studies are required to look for improvement in outcome in this group of patients.

Keywords

malignant melanoma - BRAF mutation - dabrafenib - trametinib


Publikationsverlauf

Artikel online veröffentlicht:
24. November 2021

© 2021. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Ali Z, Yousaf N, Larkin J. Melanoma epidemiology, biology and prognosis. EJC Suppl 2013; 11 (02) 81-91
    CrossrefPubMedGoogle Scholar
  • 2 Ugurel S, Röhmel J, Ascierto PA. et al Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017. Eur J Cancer 2017; 83: 247-257
    CrossrefPubMedGoogle Scholar
  • 3 Lokhandwala PM, Tseng L-H, Rodriguez E. et al Clinical mutational profiling and categorization of BRAF mutations in melanomas using next generation sequencing. BMC Cancer 2019; 19 (01) 665
    CrossrefPubMedGoogle Scholar
  • 4 Hauschild A, Grob J-J, Demidov LV. et al Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380 (9839) 358-365
    CrossrefPubMedGoogle Scholar
  • 5 Chapman PB, Hauschild A, Robert C. et al BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364 (26) 2507-2516
    CrossrefPubMedGoogle Scholar
  • 6 Carnahan J, Beltran PJ, Babij C. et al Selective and potent Raf inhibitors paradoxically stimulate normal cell proliferation and tumor growth. Mol Cancer Ther 2010; 9 (08) 2399-2410
    CrossrefPubMedGoogle Scholar
  • 7 Viros A, Milagre C, Trunzer K. et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med 2012; 366: 207-215
    CrossrefPubMedGoogle Scholar
  • 8 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) 1877-1888
    CrossrefPubMedGoogle Scholar
  • 9 Larkin J, Ascierto PA, Dréno B. et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 2014; 371 (20) 1867-1876
    CrossrefPubMedGoogle Scholar
  • 10 Long GV, Hauschild A, Santinami M. et al Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med 2017; 377 (19) 1813-1823
    CrossrefPubMedGoogle Scholar
  • 11 Common Terminology Criteria for Adverse Events (CTCAE) Protocol development CTEP. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. Accessed on September 6, 2021
  • 12 Schwartz LH, Litière S, de Vries E. et al RECIST 1.1-Update and clarification: from the RECIST committee. Eur J Cancer 2016; 62: 132-137
    CrossrefPubMedGoogle Scholar
  • 13 IARC. 356-india-fact-sheets.pdf. Available at: https://gco.iarc.fr/today/data/factsheets/populations/356-india-fact-sheets.pdf. Assessed May 20, 2021
  • 14 Sharma K, Mohanti BK, Rath GK. Malignant melanoma: a retrospective series from a regional cancer center in India. J Cancer Res Ther 2009; 5 (03) 173-180
    CrossrefPubMedGoogle Scholar
  • 15 Radhika K, Prayaga AK, Sundaram C. A clinicopathologic study of malignant melanoma based on cytomorphology. Indian J Cancer 2016; 53 (01) 199-203
    CrossrefPubMedGoogle Scholar
  • 16 Robert C, Karaszewska B, Schachter J. et al Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 2015; 372 (01) 30-39
    CrossrefPubMedGoogle Scholar
  • 17 Takahashi A, Namikawa K, Nakano E, Yamazaki N. Real-world efficacy and safety data for dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation-positive advanced melanoma. J Dermatol 2020; 47 (03) 257-264
    CrossrefPubMedGoogle Scholar
  • 18 Robert C, Grob JJ, Stroyakovskiy D. et al Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med 2019; 381 (07) 626-636
    CrossrefPubMedGoogle Scholar