Vemurafenib-induced bilateral facial palsy

Shailesh, Fnu; Singh, Manisha; Tiwari, Upasana; Hutchins, Laura F.

doi:10.4103/0022-3859.132339

Cited by 18 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent study profiling the paradoxical activation of ERK across the BRAF inhibitors vemurafenib, dabrafenib, and encorafenib suggests that differences in the potency of pERK induction in HRAS mut , BRAF wt keratinocytes relative to the potency of pERK inhibition in BRAF V600E melanoma cells may account for the varying rates of cutaneous SCC between the compounds (29). Facial paresis has been reported in cases of patients treated with vemurafenib (30,31). Symptoms typically resolve when treatment is stopped and may be resolved with steroid treatment, suggesting a possible autoimmune mechanistic trigger.…”

Section: Discussionmentioning

confidence: 99%

Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818) in Metastatic BRAF-Mutant Melanoma

Delord

Robert

Nyakas

et al. 2017

Clinical Cancer Research

161

151

View full text Add to dashboard Cite

Encorafenib, a selective BRAF inhibitor (BRAFi), has a pharmacologic profile that is distinct from that of other clinically active BRAFis. We evaluated encorafenib in a phase I study in patients with BRAFi treatment-naïve and pretreated -mutant melanoma. The pharmacologic activity of encorafenib was first characterized preclinically. Encorafenib monotherapy was then tested across a range of once-daily (50-700 mg) or twice-daily (75-150 mg) regimens in a phase I, open-label, dose-escalation and -expansion study in adult patients with histologically confirmed advanced/metastatic -mutant melanoma. Study objectives were to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D), characterize the safety and tolerability and pharmacokinetic profile, and assess the preliminary antitumor activity of encorafenib. Preclinical data demonstrated that encorafenib inhibited BRAF V600E kinase activity with a prolonged off-rate and suppressed proliferation and tumor growth of V600E-mutant melanoma models. In the dose-escalation phase, 54 patients (29 BRAFi-pretreated and 25 BRAFi-naïve) were enrolled. Seven patients in the dose-determining set experienced dose-limiting toxicities. Encorafenib at a dose of 300 mg once daily was declared the RP2D. In the expansion phase, the most common all-cause adverse events were nausea (66%), myalgia (63%), and palmar-plantar erythrodysesthesia (54%). In BRAFi-naïve patients, the overall response rate (ORR) and median progression-free survival (mPFS) were 60% and 12.4 months [95% confidence interval (CI), 7.4-not reached (NR)]. In BRAFi-pretreated patients, the ORR and mPFS were 22% and 1.9 months (95% CI, 0.9-3.7). Once-daily dosing of single-agent encorafenib had a distinct tolerability profile and showed varying antitumor activity across BRAFi-pretreated and BRAFi-naïve patients with advanced/metastatic melanoma. .

show abstract

Section: Discussionmentioning

confidence: 99%

Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818) in Metastatic BRAF-Mutant Melanoma

Delord

Robert

Nyakas

et al. 2017

Clinical Cancer Research

161

151

View full text Add to dashboard Cite

show abstract

“…With regard to the first case, in literature, there are only few reported cases of bilateral facial palsy or acute polyradiculoneuropathy in patients treated with Vemurafenib-and Cobimetinib-combined treatment [5][6][7][8][9]. The distinctive trait of our patient is that she developed both the polyradiculoneuropathy and the bilateral cranial nerves involvement 3 years after the beginning of Vemurafenib and 1 year after the combined treatment, while the other cases developed polyradiculoneuropathy or bilateral facial palsy and generally few months after the start of therapy (4-9 weeks).…”

Section: Discussionmentioning

confidence: 99%

Neuromuscular complications following targeted therapy in cancer patients: beyond the immune checkpoint inhibitors. Case reports and review of the literature

et al. 2020

View full text Add to dashboard Cite

Introduction In the last years, many new drugs have been developed targeting different oncology pathways, overall improving both quality of life and survival in several malignancies. However, the increase of those therapies is associated with novel toxicities, mainly immune-related adverse events (irAEs), never observed before. Different irAEs are now well characterized, and, among them, neuromuscular complications, following immune checkpoint inhibitor (ICPi) therapy, are increasingly studied and described. However, there are also neurological complications related to the use of other targeted therapies, less known and probably underestimated. Herein we describe two oncological patients who developed neuromuscular diseases after administration of targeted therapies, different from ICPi. Case reports The first patient was treated with the combination of Vemurafenib and Cobimetinib, BRAF and MEK inhibitors, respectively, for a cutaneous melanoma. One year after the beginning of the combined treatment, she developed a sub-acute motor neuropathy with predominant cranial nerve involvement. She was successfully treated with methylprednisolone. The second patient received therapy with Imatinib, tyrosine kinase inhibitor and precursor of the targeted therapy, for a gastrointestinal stromal tumour. Few days after the first administration, he developed generalized myasthenia gravis with respiratory failure. Clinical remission was obtained with plasma-exchange, intravenous immunoglobulins and steroids. Discussion and Conclusion We strengthen the relevance of neuromuscular complications which may occur long after treatment start or in patients receiving not only the latest ICPi but also "older" and apparently better-known targeted therapies. Also in the latter cases, an immune-mediated "off-target" pathogenic mechanism can be hypothesized, and consequences can be life threatening, if not promptly diagnosed and appropriately managed.

show abstract

“…Previous reports described 4 patients with unilateral or synchronous bilateral facial nerve palsy after start of vemurafenib, which disappeared after vemurafenib discontinuation or start of corticosteroids. [3][4][5] The exact underlying mechanism of vemurafenib-induced facial nerve palsy and acute polyneuropathy remains unclear. The response to corticosteroids in our patient and previously reported patients suggests an immune-mediated effect.…”

Section: Discussionmentioning

confidence: 99%

Acute polyneuropathy in a metastatic melanoma patient treated with vemurafenib and cobimetinib

et al. 2017

View full text Add to dashboard Cite

Vemurafenib-induced bilateral facial palsy

Cited by 18 publications

References 5 publications

Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818) in Metastatic BRAF-Mutant Melanoma

Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818) in Metastatic BRAF-Mutant Melanoma

Neuromuscular complications following targeted therapy in cancer patients: beyond the immune checkpoint inhibitors. Case reports and review of the literature

Acute polyneuropathy in a metastatic melanoma patient treated with vemurafenib and cobimetinib

Contact Info

Product

Resources

About