1226PD - Five-year Efficacy and Safety Update From METRIC: Trametinib vs Chemotherapy in Patients with BRAF V600E/K–Mutant Advanced or Metastatic Melanoma

Date 11 September 2017
Event ESMO 2017 Congress
Session Melanoma and other skin tumours
Topics Anti-Cancer Agents & Biologic Therapy
Cancer in Adolescents
Melanoma and other Skin Tumours
Presenter Dirk Schadendorf
Citation Annals of Oncology (2017) 28 (suppl_5): v428-v448. 10.1093/annonc/mdx377
Authors D. Schadendorf1, K.T. Flaherty2, P. Nathan3, P. Hersey4, C. Garbe5, M. Milhem6, L. Demidov7, P. Mohr8, J.C. Hassel9, P. Rutkowski10, R. Dummer11, J. Utikal12, F. Kiecker13, J. Larkin14, A. D’Amelio Jr15, Y. Huang15, B. Mookerjee15, C. Robert16
  • 1Department Of Dermatology, University Hospital Essen, 45122 - Essen/DE
  • 2Medicine, Massachusetts General Hospital Cancer Center, 02114 - Boston/US
  • 3Department Of Medical Oncology, Mount Vernon Cancer Centre, HA6 2RN - Northwood/GB
  • 4Melanoma Oncology And Immunology, University of Sydney, Sydney/AU
  • 5Department Of Dermatology, University Medical Center, 72076 - Tübingen/DE
  • 6Hematology, Oncology And Blood & Marrow Transplantation, University of Iowa Hospital and Clinics, Iowa/US
  • 7Department Of Dermatology, N. N. Blokhin Russian Cancer Research Center, Moscow/RU
  • 8Department Of Dermatology, Elbeklinikum Buxtehude, Buxtehude/DE
  • 9Department Of Dermatology And Nct, University Hospital Heidelberg and National Center for Tumor Diseases, Heidelberg/DE
  • 10Department Of Soft Tissue/bone Sarcoma And Melanoma, The Maria Sklodowska-Curie Memorial Institute and Oncology Centre, 02-781 - Warsaw/PL
  • 11Department Of Dermatology, University Hospital Zürich-Dermatology, 8091 - Zürich/CH
  • 12Dermatooncology, German Cancer Research Center, 69120 - Heidelberg/DE
  • 13Clinic Of Dermatology, Charité University Hospital, 10117 - Berlin/DE
  • 14Skin Unit, Royal Marsden Hospital, London, United Kingdom, London/GB
  • 15Global Oncology, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey/US
  • 16Department Of Medicine, Gustave Roussy and INSERM Unité 981, 94800 - Villejuif–Paris Sud/FR

Abstract

Background

BRAF mutations are found in 50% of patients (pts) with advanced melanoma. Previously, the METRIC trial (NCT01245062) demonstrated that the MEK inhibitor trametinib (T) increased PFS in this population of patients with a clinical benefit that could last ≥ 2 yrs in some pts. We report findings from the 5-year follow-up analysis

Methods

METRIC is an open-label, randomized Ph3 study of pts who received ≤ 1 prior regimen of chemotherapy (C) for histologically confirmed unresectable stage IIIC or IV cutaneous BRAF V600E/K–mutant metastatic melanoma (MM). Pts were randomized (2:1) to T (2 mg/day) or intravenous C (dacarbazine [1000 mg/m2] or paclitaxel [175 mg/m2] every 3 wks). Pts were stratified according to baseline lactate dehydrogenase level and previous C for advanced disease. Pts who progressed on C were allowed to crossover and receive T. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), duration of response and safety.

Results

322 pts (V600E: 281, 600K: 40, V600E/K mutation: 1) were enrolled (T: 214; C: 108). At data cutoff (Dec 16, 2016), median follow-up was 12.3 months (mo). The median OS for the T arm was 15.6 mo vs 11.3 mo for the C arm (HR = 0.84 [95% CI, 0.63–1.11], P = 0.19). Landmark OS for the T arm vs the C arm at 1, 2, 3, and 5 yrs were 60.9% vs 49.6%; 32.0% vs 29.4%; 20.6% vs 22.6%; and 13.3% vs 17.0%, respectively. Most pts (n = 70, 65%) in the C arm crossed over and received T. Median time to crossover was 3.1 (1–20) mo; median duration of follow-up after crossover was 8.8 (0–67) mo. Among pts who received post-tx anti-cancer therapy (n = 208), most received targeted therapy (n = 118), immunotherapy (n = 90), or C (n = 84). No new safety signals were observed.

Conclusions

This is the longest reported follow up for T monotherapy in pts with BRAF V600E/K–mutant MM and demonstrates that some of these pts experience long-term benefit with targeted therapy. Pts with extended follow-up after initiation of T, contributed to long-term survival for those randomized to the C arm.

Clinical trial identification

NCT01245062

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

Funding

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

Disclosure

D. Schadendorf: Reports grants and personal fees from Novartis, MSD/Merck, Amgen, GSK, Sysmex, Boehringer Ingelheim, Bristol-Myers Squibb, outside the submitted work K.T. Flaherty: Consulted for Novartis in relation to this abstract P. Nathan: Reports personal fees from Novartis, outside the submitted work. C. Garbe: Reports grants and personal fees from Novartis, during the conduct of the study; personal fees from Amgen, MSD, Philogen, grants and personal fees from Roche and Bristol-Myers Squibb, outside the submitted work. P. Mohr: Reports personal fees and other from Novartis, during the conduct of the study; personal fees and other from Amgen, grants, personal fees and other Bristol-Myers Squibb, MSD, Merck, Roche, outside the submitted work. J.C. Hassel: Reports other from GSK, during the conduct of the study; personal fees from Bristol-Myers Squibb, MSD, Roche, Novartis, Amgen, MSD, other from MSD, Bristol-Myers Squibb, Novartis, outside the submitted work. P. Rutkowski: Reports personal fees from Novartis, Bristol-Myers Squibb, Roche, MSD, GSK, Amgen, outside the submitted work. R. Dummer: Receives research funding and and has a consultant or has advisory board relationship with Novartis, MSD, Bristol-Myers Squibb, Roche, GSK, Amgen, outside the submitted work J. Utikal: Reports to be on the advisory board and has received travel support from Amgen, Bristol-Myers Squibb, GSK, MSD, Novartis and Roche F. Kiecker: Reports personal fees from Amgen, personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Roche, outside the submitted work. J. Larkin: Research support, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Consultancy: Eisai, Bristol-Myers Squibb, MSD, GSK, Kymab, Pfizer, Novartis, Roche/Genentech, Secarna, Pierre Fabre, EUSA, Support, NIHR RM/ICR Biomedical Research Centre for Cancer A. D’Amelio Jr: Reports personal fees from Novartis Pharmaceuticals, during the conduct of the study; other from Novartis Pharmaceuticals, other from GlaxoSmithKline, outside the submitted work Y. Huang: Employee of Novartis. B. Mookerjee: Employee of Novartis, stock and other ownership, Novartis, GSK, Incyte, AstraZeneca C. Robert: Participated in advisory boards for Roche, GSK, Merck, Novartis, Amgen, Bristol-Myers Squibb, Novartis. All other authors have declared no conflicts of interest.