Association Between Baseline Disease Characteristics and Relapse-Free Survival (RFS) in Patients (pts) with BRAF V600–Mutant Resected Stage III Melanoma Treated with Adjuvant Dabrafenib (D) + Trametinib (T) or Placebo (PBO)

November 2019 Vol 10, No 11
Dirk Schadendorf, MD
University Hospital Essen, Germany and German Cancer Consortium, Germany
Reinhard Dummer, MD
University Hospital Zürich Skin Cancer Center, Switzerland
Axel Hauschild, MD
University Hospital Schleswig-Holstein, Germany
Mario Santinami, MD
Fondazione Istituto Nazionale Tumori, Italy
Victoria Atkinson, MD
Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Australia
Mario Mandalà, MD
Papa Giovanni XXIII Cancer Center Hospital, Italy
Vanna Chiarion Sileni, MD
Melanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Italy
James Larkin, MD, PhD
Royal Marsden NHS Foundation Trust, United Kingdom
Marta Nyakas, MD
Oslo University Hospital, Norway
Caroline Dutriaux, MD
Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, France
Andrew Haydon, MD, PhD
The Alfred Hospital, Australia
Laurent Mortier, MD
Université de Lille, INSERM U 1189, France
Caroline Robert, MD, PhD
Institut Gustave Roussy and Paris-Sud University, France
Jacob Schachter, MD
Ella Lemelbaum Institute for Immuno-Oncology and Melanoma, Sheba Medical Center, Tel-Hashomer, and Sackler Medical School, Tel-Aviv University, Israel
Christine-Elke Ortmann, MS
Novartis Pharma AG, Switzerland
Egbert de Jong, MD
Novartis Pharma AG, Switzerland
Eduard Gasal, MD
Novartis Pharmaceuticals Corporation, East Hanover, NJ
Richard Kefford, MD, PhD
Macquarie University, Melanoma Institute Australia, Westmead Hospital, and The University of Sydney
John M. Kirkwood, MD
Melanoma Program, UPMC Hillman Cancer Center, University of Pittsburgh, PA
Georgina V. Long, MD, PhD
Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals

Background: In the COMBI-AD trial (NCT01682083), 12 months of adjuvant D+T led to significant improvement of RFS versus PBO (hazard ratio [HR], 0.47; P <.001) in pts with resected BRAF V600–mutant stage III melanoma; 3- and 4-year RFS rates were 59% and 54%, respectively. Previous results showed consistent treatment benefit across baseline disease stage according to American Joint Committee on Cancer edition 7 or 8.

Objectives: Here, we further explored the association between baseline disease characteristics and RFS to identify pt subgroups likely to benefit from adjuvant treatment.

Methods: Randomized pts with completely resected BRAF V600E/K–mutant stage III melanoma received 12 months of adjuvant D (150 mg BID) + T (2 mg QD) or PBO. Within each subgroup, predictive value was explored using Kaplan-Meier analysis, and hazard ratios (HRs) were calculated using a Pike estimator.

Results: Minimum follow-up was 40 months for 870 enrolled pts (D+T, 438; PBO, 432). Kaplan-Meier analysis demonstrated treatment benefit across all subgroups analyzed. Assessment of RFS by extent of primary tumor (T stage) showed consistent benefit favoring D+T versus PBO (HR [95% CI]; T1, 0.42 [0.25-0.70]; T2, 0.51 [0.34-0.76]; T3, 0.55 [0.39-0.77]; T4, 0.42 [0.29-0.60]). HRs by nodal burden (N stage) also showed consistent treatment benefit (N1, 0.52 [95% CI, 0.37-0.72]; N2, 0.38 [95% CI, 0.28-0.53]; N3, 0.58 [95% CI, 0.41-0.83]). Substantial treatment benefit was observed in pts with baseline in-transit metastases (HR, 0.45 [95% CI, 0.24-0.82]) and those with no in-transit metastases detected at baseline (HR, 0.49 [95% CI, 0.40-0.60]). When RFS was assessed according to melanoma presentation, treatment benefit favoring D+T versus PBO was observed in pts with superficial spreading melanoma (HR, 0.48 [95% CI, 0.35-0.66]) and those with nodular melanoma (HR, 0.53 [95% CI, 0.37-0.75]).

Conclusions: These results confirm earlier findings showing that treatment benefit with adjuvant D+T versus PBO is independent of baseline factors.

Note: The COMBI-AD study was sponsored by GlaxoSmithKline; dabrafenib and trametinib are assets of Novartis AG as of March 2, 2015.

This abstract was accepted and previously presented at: American Society of Clinical Oncology Annual Meeting; June 1-3, 2019; Chicago, IL. All rights reserved.

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