Dabrafenib–Trametinib Has ‘Robust Clinical Activity’ In BRAF-Mutated Anaplastic Thyroid Cancer

Combined BRAF–MEK inhibition with dabrafenib and trametinib could be an option for patients with BRAF V600E-mutated anaplastic thyroid cancer

medwireNews: The combination of dabrafenib and trametinib elicits durable responses, prolongs survival and is well tolerated in patients with locally advanced or metastatic anaplastic thyroid cancer positive for the BRAF V600E mutation, phase II results signal.

“This is the first regimen to demonstrate robust clinical activity” in these patients, who generally have poor outcomes in the absence of systemic therapies with clinical benefit, comment Bhumsuk Keam, from Seoul National University Hospital in South Korea, and colleagues in the Journal of Clinical Oncology.

They add: “These data indicate that tumor mutation screening should be performed for patients with [anaplastic thyroid cancer] as it has the potential to transform outcomes for these patients.”

The team reports on the outcomes of 16 advanced anaplastic thyroid cancer patients who formed part of a multi-histology trial investigating the effects of treatment with the BRAF inhibitor dabrafenib given at a dose of 150 mg twice a day plus the MEK inhibitor trametinib given at a dose of 2 mg/day, both used until disease progression, unacceptable toxicity or death.

During a median follow-up of 47 weeks, one patient had a complete response and 10 had partial responses, giving an investigator-assessed overall response rate of 69%. Seven responses were ongoing at the time of data analysis and the median duration of response had not been reached.

The median progression-free and overall survival (OS) times were also unreached, but the corresponding estimated 12-month rates were 79% and 80%.

The researchers describe the OS rate as “remarkable” compared with “the historical rate of 20% to 40% for this patient population.”

They add that the regimen was well tolerated and that the safety profile “was similar to previous reports in advanced or metastatic melanoma and non–small-cell lung cancer.”

In all, half of the anaplastic thyroid cancer patients experienced an adverse event of grade 3 or 4, with anaemia the most frequently observed event, occurring in two patients, followed by fatigue, diarrhoea and hyperglycaemia in one patient each.

Treatment-related serious toxicity occurred in three patients, a case each of acute kidney injury and rhabdomyolysis, pyrexia and hyponatraemia.

“Although this study evaluated a small number of patients and independent confirmation of pathology was not performed […], these results are nonetheless noteworthy because of the unmet need for an effective therapy for this rare patient population”, say Bhumsuk Keam et al.

“These results require confirmation in additional clinical studies, although conducting a randomized trial in this setting is challenging, given the rarity of the patient population and the loss of clinical equipoise.”

Reference

Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600–mutant anaplastic thyroid cancer. J Clin Oncol; Advance online publication 26 October 2017. doi:10.1200/JCO.2017.73.6785

medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group