Open AccessIdentifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial
Author(s) -
Patricia LoRusso,
Aleksandar Sekulić,
Jeffrey A. Sosman,
Winnie S. Liang,
John D. Carpten,
David W. Craig,
David B. Solit,
Alan H. Bryce,
Jeffrey Kiefer,
Jessica Aldrich,
Sara Nasser,
Rebecca F. Halperin,
Sara A. Byron,
Mary Jo Pilat,
Scott A. Boerner,
Diane E. Durecki,
William P.D. Hendricks,
Daniel Enríquez,
Tyler Izatt,
Jonathan J. Keats,
Christophe Legendre,
Svetomir N. Markovic,
Amy Weise,
Fatima Naveed,
Jessica Schmidt,
Gargi D. Basu,
Shobana Sekar,
Jonathan Adkins,
Erica E. Tassone,
Karthigayini Sivaprakasam,
Victoria Zismann,
Valerie Calvert,
Emanuel F. Petricoin,
Leslie A. Fecher,
Christopher D. Lao,
Joseph P. Eder,
Nicholas J. Vogelzang,
Jane Perlmutter,
Mark Gorman,
Barbara Manica,
Lisa Fox,
Nicholas J. Schork,
Daniel Zelterman,
Michelle DeVeaux,
Richard W. Joseph,
C. Lance Cowey,
Jeffrey M. Trent
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0248097
Subject(s) - medicine , metastatic melanoma , oncology , melanoma , clinical trial , mek inhibitor , immunotherapy , targeted therapy , disease , trametinib , randomized controlled trial , cancer research , cancer , biology , mapk/erk pathway , genetics , kinase
Although combination BRAF and MEK inhibitors are highly effective for the 40–50% of cutaneous metastatic melanomas harboring BRAF V600 mutations, targeted agents have been ineffective for BRAF V600 wild-type (wt) metastatic melanomas. The SU2C Genomics-Enabled Medicine for Melanoma Trial utilized a Simon two-stage optimal design to assess whether comprehensive genomic profiling improves selection of molecular-based therapies for BRAF V600 wt metastatic melanoma patients who had progressed on standard-of-care therapy, which may include immunotherapy. Of the response-evaluable patients, binimetinib was selected for 20 patients randomized to the genomics-enabled arm, and nine were treated on the alternate treatment arm. Response rates for 27 patients treated with targeted recommendations included one (4%) partial response, 18 (67%) with stable disease, and eight (30%) with progressive disease. Post-trial genomic and protein pathway activation mapping identified additional drug classes that may be considered for future studies. Our results highlight the complexity and heterogeneity of metastatic melanomas, as well as how the lack of response in this trial may be associated with limitations including monotherapy drug selection and the dearth of available single and combination molecularly-driven therapies to treat BRAF V600 wt metastatic melanomas.