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Sustained Tumor Control With MAPK Inhibition in BRAF V600–Mutant Adult Glial and Glioneuronal Tumors

Sustained Tumor Control With MAPK Inhibition in BRAF V600–Mutant Adult Glial and Glioneuronal Tumors

17 août 2021Neurology

Auteurs

Giulia Berzero, Luisa Bellu, Capucine Baldini, François Ducray, David Guyon, Marica Eoli, Antonio Silvani, Caroline Dehais, Ahmed Idbaih, Nadia Younan, Ludovic Nguyen-Them, Stephan Gaillard, Francesco Pasqualetti, Coralie Lepage-Seydoux, Sakina Sekkate, Patricia Tresca, Aurélie Kas, Julie Gratieux, Samy Ammari, Edouard Saragoussi, Julien Savatovsky, Jean-Yves Delattre, Khê Hoang-Xuan, David Meyronet, Chiara Villa, Franck Bielle, Marc Sanson, Mehdi Touat, Anna Luisa Di Stefano

Résumé

Objective

To assess whether RAF and MEK inhibitors (RAFi/MEKi) can provide long-term clinical benefit in adult patients withBRAFV600–mutant glial and glioneuronal tumors (GGNTs), we analyzed tumor response and long-term outcome in a retrospective cohort.

Methods

We performed a retrospective search in the institutional databases of 6 neuro-oncology departments for adult patients with recurrent or disseminatedBRAFV600–mutant GGNTs treated with RAFi/MEKi.

Results

Twenty-eight adults with recurrent or disseminatedBRAFV600–mutant gangliogliomas (n = 9), pleomorphic xanthoastrocytomas (n = 9), and diffuse gliomas (n = 10) were included in the study. At the time that treatment with RAFi/MEKi was started, all tumors displayed radiologic features of high-grade neoplasms. Thirteen patients received RAFi as single agents (vemurafenib [n = 11], dabrafenib [n = 2]), and 15 received combinations of RAFi/MEKi (vemurafenib + cobimetinib [n = 5], dabrafenib + trametinib [n = 10]). Eleven patients achieved a partial or complete response (11 of 28, 39%), with a median reduction of −78% in their tumor burden. Responders experienced a median increase of 10 points in their Karnofsky Performance Status (KPS) score and a median progression-free survival of 18 months, which was longer than achieved with first-line treatment (i.e., 7 months,p= 0.047). Responders had better KPS score (p= 0.018) and tended to be younger (p= 0.061) and to be treated earlier (p= 0.099) compared to nonresponders. Five patients were rechallenged with RAFi/MEKi at progression, with novel tumor responses in 2. On univariate and multivariate analyses, response to RAFi/MEKi was an independent predictor of overall survival.

Conclusions

Our study highlights the long-term clinical benefits of RAFi/MEKi in adult patients withBRAFV600–mutant GGNTs and encourages rechallenge in responders.

Classification of Evidence

This study provides Class III evidence that, for adult patients withBRAFV600-mutant GGNT, RAFi/MEKi can reduce tumor burden and provide clinical benefit.