vemurafenib
Sources réglementaires consultées
Indications approuvées
- Mélanome non résécable ou métastatique avec mutation BRAF V600E confirmée par test, et maladie d’Erdheim-Chester avec mutation BRAF V600. Ne pas utiliser dans les tumeurs BRAF de type sauvage.
Contre-indications
Absolues
- CIMA : hypersensibilité à la substance active ou aux excipients ; l’étiquette FDA n’établit aucune contre-indication formelle.
Mises en garde cliniques
- Contrôler ECG et K/Mg/Ca au départ, au jour 15, mensuellement pendant 3 mois puis tous les 3 mois. Surveiller hypersensibilité/DRESS, SCAR, foie mensuellement, uvéite, reins et radiosensibilisation ou rappel. — OpenFDA, set_id 38eea320-7e0c-485a-bc30-98c3c45e2763
- Effectuer un examen dermatologique initial, tous les 2 mois et pendant 6 mois après pour carcinomes épidermoïdes/kératoacanthomes, nouveaux mélanomes et autres cancers. Utiliser une photoprotection SPF ≥30. — OpenFDA, set_id 38eea320-7e0c-485a-bc30-98c3c45e2763
Interactions médicamenteuses
- SévèreModulateurs du CYP3A
Mécanisme: Ils peuvent modifier l’exposition au vémurafénib.
Recommandation: Éviter inhibiteurs et inducteurs puissants. Si un inducteur est inévitable, augmenter chaque prise de 240 mg puis revenir à la dose antérieure 2 semaines après son arrêt.
OpenFDA, set_id 38eea320-7e0c-485a-bc30-98c3c45e2763
- SévèreSubstrats CYP1A2 ou P-gp à marge étroite
Mécanisme: Le vémurafénib peut augmenter leur exposition.
Recommandation: Éviter ou réduire le substrat et surveiller la toxicité.
OpenFDA, set_id 38eea320-7e0c-485a-bc30-98c3c45e2763
Effets indésirables
Communs (≥1%)
arthralgie · éruption cutanée · alopécie · fatigue · réaction de photosensibilité · nausées · prurit
Grossesse et allaitement
Peut provoquer une atteinte fœtale. Les femmes doivent utiliser une contraception pendant et 2 semaines après. Ne pas allaiter pendant ni 2 semaines après.
Bibliographie récente (PubMed)
Craniopharyngiomas, primary brain tumors of the pituitary-hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF-MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy. Eligible patients who had papillary craniopharyngiomas that tested positive for BRAF mutations, had not undergone radiation therapy previously, and had measurable disease received the BRAF-MEK inhibitor combination vemurafenib-cobimetinib in 28-day cycles. The primary end point of this single-group, phase 2 study was objective response at 4 months as determined with the use of centrally determined volumetric data. Of the 16 patients in the study, 15 (94%; 95% confidence interval [CI], 70 to 100) had a durable objective partial response or better to therapy. The median reduction in the volume of the tumor was 91% (range, 68 to 99). The median follow-up was 22 months (95% CI, 19 to 30) and the median number of treatment cycles was 8. Progression-free survival was 87% (95% CI, 57 to 98) at 12 months and 58% (95% CI, 10 to 89) at 24 months. Three patients had disease progression during follow-up after therapy had been discontinued; none have died. The sole patient who did not have a response stopped treatment after 8 days owing to toxic effects. Grade 3 adverse events that were at least possibly related to treatment occurred in 12 patients, including rash in 6 patients. In 2 patients, grade 4 adverse events (hyperglycemia in 1 patient and increased creatine kinase levels in 1 patient) were reported; 3 patients discontinued treatment owing to adverse events. In this small, single-group study involving patients w
Treatment with encorafenib plus binimetinib and encorafenib monotherapy is associated with improved progression-free survival (PFS) and overall survival (OS) compared with vemurafenib in patients with BRAF V600E/K-mutant metastatic melanoma. We report results from the 7-year analysis of COLUMBUS part 1 (NCT01909453) at 99.7 months (median duration between randomization and data cutoff). 577 patients with locally advanced unresectable or metastatic BRAF V600E/K-mutant melanoma who were treatment-naive or progressed after first-line immunotherapy were randomized 1:1:1 to encorafenib 450 mg once daily (QD) plus binimetinib 45 mg twice daily (BID) (n = 192), vemurafenib 960 mg BID (n = 191), or encorafenib monotherapy 300 mg QD (n = 194). No prior BRAF/MEK inhibitor was allowed. Seven-year PFS and OS rates (95 % CI) were 21.2 % (14.7-28.4 %) and 27.4 % (21.2-33.9%) in the encorafenib plus binimetinib arm and 6.4 % (2.1-14.0 %) and 18.2 % (12.8-24.3 %) in the vemurafenib arm, respectively. Median melanoma-specific survival (95 % CI) was 36.8 months (27.7-51.5 months) in the encorafenib plus binimetinib arm and 19.3 months (14.8-25.9 months) in the vemurafenib arm. Thirty-four long-term responders (complete/partial response ongoing at 7 years) were identified across arms. This is the longest follow-up from a phase III trial of BRAF/MEK inhibitor combination in BRAF V600E/K-mutant metastatic melanoma. Safety results were consistent with the known tolerability profile of encorafenib plus binimetinib. Results support the long-term efficacy and known safety of encorafenib plus binimetinib in this population and provide new insights on long-term responders. Interactive data visualization is available at the COLUMBUS dashboard (https://clinical-trials.dimensions.ai/columbus7/).
Photosensitizing drug reactions are cutaneous eruptions that occur after exposure to ultraviolet radiation in patients using photosensitizing medications. The reactions can be broadly classified into phototoxic and photoallergic, with the former being much more common and well documented. There is an extensive list of photosensitizing medications, especially in the case of phototoxicity. The most common are amiodarone, chlorpromazine, doxycycline, hydrochlorothiazide, nalidixic acid, naproxen, piroxicam, tetracycline, thioridazine, vemurafenib, and voriconazole. Most of the medications implicated in photosensitivity share an action spectrum within the ultraviolet A range. Distinguishing between phototoxicity and photoallergy can be difficult, because some clinical overlap exists between the two disorders. It is often done based on pathogenesis, clinical presentation, and diagnosis. Management is similar for both types of reactions, with the gold standard being prevention. This review provides an overview of the photosensitizing drug reactions and highlights the similarities and differences between phototoxicity and photoallergy, as well as other photosensitizing drug reactions in the phototoxicity family including lichenoid reactions and pseudoporphyria. Hairy cell leukemia is a rare, indolent, chronic lymphoid neoplasm originating from a mature B lymphocyte. Diagnosis is based on hairy cell morphology, immunological phenotype by flow cytometry and/or immunohistochemistry in trephine biopsy, and the presence of BRAFV600E somatic mutation. In the classic form of the disease, the purine nucleoside analogues pentostatin and cladribine are recommended for the first-line treatment. These agents induce durable and unmaintained complete response in more than 70% of cases and up to 35% of patients demonstrate overall survival longer than 20 years. When rituximab is combined with cladribine in early relapse, complete response can be achieved in 89–100% of patients, with a th
Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors. To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS). A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023. Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab. The primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months. Forty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial gr