Four-month course of adjuvant dabrafenib in patients with surgically resected stage IIIC melanoma characterized by a BRAFV600E/K mutation Journal Article

Authors: Momtaz, P.; Harding, J. J.; Ariyan, C.; Coit, D. G.; Merghoub, T.; Gasmi, B.; You, D.; Viale, A.; Panageas, K. S.; Samoila, A.; Postow, M. A.; Wolchok, J. D.; Chapman, P. B.
Article Title: Four-month course of adjuvant dabrafenib in patients with surgically resected stage IIIC melanoma characterized by a BRAFV600E/K mutation
Abstract: Background: We tested the hypothesis that a 4-month course of adjuvant dabrafenib in stage IIIC BRAF-mutated melanoma would improve 2 year RFS from 24% to 51%, and that tumor-derived cell free DNA (cfDNA) in plasma would correlate with and predict recurrence. Methods: Patients with stage IIIC BRAF V600E/K mutated melanoma who were free of disease after surgical resection received 4 months of adjuvant dabrafenib. Patients were evaluated with imaging at baseline, at the end of cycles 2, 4, 6, then every 3 months until disease relapse or 2 years, whichever came first. Serial blood samples were collected for evaluation of cfDNA at the same time. Results: 21/23 patients enrolled were evaluable; 2 patients withdrew consent during the first week of treatment. The 2 year RFS was 28.6% (95% CI 12-48%). The estimated overall survival at 2 years was 78% (95% CI 51-91%). cfDNA detection had a 53% sensitivity in relapsing patients but cfDNA detection did not provide leadtime advantage over CT scanning. Conclusion: A 4-month course of adjuvant dabrafenib did not result in a detectable improvement in 2-year RFS. cfDNA was less sensitive than standard CT imaging and did not provide a lead-time advantage in detecting relapse. © Momtaz et al.
Keywords: adult; cancer survival; clinical article; controlled study; human tissue; treatment response; aged; middle aged; young adult; gene mutation; overall survival; fatigue; diarrhea; drug efficacy; drug safety; hypophosphatemia; treatment duration; cancer adjuvant therapy; cancer staging; outcome assessment; sensitivity and specificity; anorexia; melanoma; phase 2 clinical trial; anemia; leukopenia; nausea; neuropathy; vomiting; myalgia; arthralgia; chill; fever; pruritus; rash; drug cost; insomnia; dna; headache; hot flush; cancer epidemiology; dyspepsia; hand foot syndrome; dry skin; alopecia; dna determination; photophobia; blurred vision; dysgeusia; sore throat; recurrence free survival; hypertransaminasemia; photosensitivity disorder; relapse-free survival; dabrafenib; faintness; human; male; female; article; digital pcr; x-ray computed tomography; cfdna; abducens nerve disease
Journal Title: Oncotarget
Volume: 8
Issue: 62
ISSN: 1949-2553
Publisher: Impact Journals  
Date Published: 2017-12-01
Start Page: 105000
End Page: 105010
Language: English
DOI: 10.18632/oncotarget.21072
PROVIDER: scopus
PMCID: PMC5739615
PUBMED: 29285228
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Jedd D Wolchok
    656 Wolchok
  2. Taha Merghoub
    201 Merghoub
  3. Michael Andrew Postow
    185 Postow
  4. James Joseph Harding
    66 Harding
  5. Paul Chapman
    246 Chapman
  6. Katherine S Panageas
    327 Panageas
  7. Charlotte Eielson Ariyan
    77 Ariyan
  8. Agnes Viale
    205 Viale
  9. Daniel Coit
    415 Coit
  10. Aliaksandra Samoila
    13 Samoila
  11. Daoqi You
    20 You
  12. Billel Gasmi
    11 Gasmi
  13. Parisa   Momtaz
    16 Momtaz