Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Melanoma and other skin tumours

3349 - Phase 2 study of neoadjuvant dabrafenib + trametinib (D+T) for resectable stage IIIB/C BRAF V600 mutant melanoma.


11 Sep 2017


Melanoma and other skin tumours


Cytotoxic Therapy;  Cancers in Adolescents and Young Adults (AYA);  Melanoma


Alexander Menzies


Annals of Oncology (2017) 28 (suppl_5): v428-v448. 10.1093/annonc/mdx377


A.M. Menzies1, M. Gonzalez1, A. Guminski1, O. Nieweg2, K. Shannon2, J.F. Thompson2, R. Kefford3, S. Ch'Ng2, J. Stretch1, A.J. Spillane2, J. Lee4, H. Lee5, R. Kapoor6, L. Emmett7, H. Rizos8, R.P. Saw2, R.A. Scolyer9, G.V. Long1

Author affiliations

  • 1 Medical Oncology, Melanoma Institute Australia, University of Sydney, 2060 - North Sydney/AU
  • 2 Surgical Oncology, Melanoma Institute Australia, 2060 - Sydney/AU
  • 3 Medical Oncology, Macquarie University, 2109 - Macquarie Park/AU
  • 4 Medical Oncology, Macquarie University, Sydney/AU
  • 5 Pathology, Melanoma Institute Australia, Sydney/AU
  • 6 Radiology, Royal Prince Alfred Hospital, Sydney/AU
  • 7 Nuclear Medicine, St Vincent's Hospital, Sydney/AU
  • 8 Biology, Macquarie University, Sydney/AU
  • 9 Pathology, Royal Prince Alfred Hospital, 2050 - Camperdown/AU


Abstract 3349


Combination D+T improves the overall survival (OS) of patients (pts) with BRAF V600 mutant advanced melanoma, and an adjuvant trial is in progress (NCT01682083). We sought to explore neoadjuvant D+T for pts with bulky but resectable stage III melanoma.


In this phase 2 study, 35 pts received standard dose D+T for 12 wks prior to complete resection of the pre-therapy tumour bed (RES), then 40 wks of further D+T. Eligible pts had ECOG PS ≤ 1 with histologically confirmed resectable bulky AJCC v7 stage IIIB/C BRAF V600 mutant melanoma. CT and PET scans were performed at baseline and 12 wks just prior to RES for RECIST and metabolic complete response (rCR and mCR respectively). CT monitoring was continued 12 wkly thereafter to 2 yrs then 6 monthly to 3 yrs. Biopsies were taken at baseline and wk 1. The primary endpoints were the complete pathological response (pCR) and RECIST response rate (rRR) at wk 12. Secondary endpoints were surgical morbidity, mCR, relapse free survival (RFS), OS, toxicity and translational endpoints.


At data cut 18th April 2017, 35 had commenced D+T. 33 had reached RES (27 stage IIIC [8 in-transit only], 6 IIIB; 32 V600E, 1 V600K; 12 LDH >ULN). At RES, 17/33 (52%) had pCR, 16 (48%) had rCR (rRR 88%), and 16 (48%) had mCR. The pathologic response was discordant with RECIST response in 7 (21%) pts and metabolic response in 9 (27%) pts; only 11 (65%) pts with pCR had rCR and mCR. No pt discontinued D+T and no pt progressed during the neoadjuvant period, D+T did not make surgery more difficult in any pt, and in 16 (48%) surgery was deemed easier. Median F/U post RES was 12.1 mo (95% CI 8.8-14.8). 12 (36%) pts had recurred (median 12.9 mo), 4 while on D+T, 6 with prior pCR, 8 at distant sites, and 1 pt had died. 26 (79%) pts developed drug fever. 18 (55%) had ≥ 1 surgical complication post RES; 11 had a wound infection requiring antibiotics, 5 had a seroma, 2 bled. Updated data will be presented including tumour biopsy and and ctDNA biomarker data.


Neoadjuvant D+T has a high response rate and high pCR rate in resectable stage III melanoma. Surgical complication rates were consistent with historic controls and stage of disease.

Clinical trial identification


Legal entity responsible for the study

Melanoma Institute Australia




A.M. Menzies: Advisory board - MSD, Novartis, Chugai, Pierre Fabre. Honoraria - Bristol-Myers Squibb, Roche G.V. Long: Advisory board - Bristol-Myers Squibb, MSD, Novartis, Amgen, Pierre Fabre. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.