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Vemurafenib Demonstrates Antitumor Activity in Papillary Thyroid Cancer

Andrew J. Roth
Published: Friday, Oct 18, 2013

Papillary Carcinoma of the Thyroid

Scrape cytology illustrating features of papillary carcinoma of the thyroid.

In a phase II clinical trial, the BRAF inhibitor vemurafenib demonstrated antitumor activity in patients with BRAFV600E-mutated papillary thyroid cancer who were either tyrosine kinase inhibitor (TKI) treatment naïve or had received prior TKI treatments. These findings were reported on September 28 at the European Cancer Congress 2013.

In this 10-center worldwide trial, median progression-free survival (PFS) in treatment-naïve patients treated with vemurafenib was 15.6 months. Though these data were encouraging, the authors of the study wrote, there remains a need for further evaluation.

“Approximately 50% of patients with PTC have tumors with activating BRAFV600E mutations, an established indicator of poor prognosis in PTC, which led to the hypothesis that inhibition of mutated BRAF kinase may be of clinical benefit,” the authors of the study wrote.

In the trial, 51 patients had undergone prior surgery and RAI treatment. Patients were assigned to two cohorts: those who were TKI treatment naïve (n=26) and those who had been previously treated with TKIs (n=25). Three (12%) patients in the TKI treatment-naïve arm and 7 (28%) patients in the TKI-treated arm had received chemotherapy previously. Also in the TKI-treated cohort, 21 (84%) patients had received prior sorafenib.1

Both cohorts received oral vemurafenib at 960 mg tablets twice daily and were assessed for tumor response after every 8 weeks of treatment.

In the analysis, the best overall response rate (BORR), the primary endpoint, was 35% in the TKI treatment-naïve arm and 26% in the TKI-treated arm. No complete responses (CR) were reported and all BORR were partial responses (PR). The clinical benefit rate (CR + PR + stable disease ≥ 6 months) was 58% in the TKI treatment-naïve arm and 36% in the TKI-treated arm. Median PFS at six months after enrollment of the last patient (preplanned primary endpoint analysis) was 15.6 months in the TKI treatment-naïve arm (95% CI: 11.2-NR) and 6.8 months in the TKI-treated arm (95% CI: 5.38-NR). A total of 18 patients discontinued treatment due to progressive disease.

Vemurafenib, which is approved by the FDA for the treatment of late-stage melanoma, demonstrated a similar toxicity profile in this trial of patients with PTC. There were, however, higher rates of weight loss, dysgeusia, anaemia, increased creatinine, and liver laboratory abnormalities in PTC.

Across several previous studies, the BRAFV600E mutation has been reported to be associated with several negative prognostic clinicopathologic features as well as an increase in overall mortality in patients with PTC. However, inconsistent study results have prolonged a definitive conclusion on the prognostic role of the gene.

“A phase I trial with vemurafenib, an inhibitor of oncogenic BRAF kinase, showed response or stable disease in 3 patients with BRAFV600E-mutated PTC,” the authors wrote. “We conducted an open-label phase II trial to determine activity of vemurafenib in patients with BRAFV600E-mutated PTC.”

In a poster presentation at the 83rd Annual Meeting of the American Thyroid Association, researchers from the MD Anderson Cancer Center reported on a series of patients with advanced metastatic BRAFV600E-mutated PTC treated with vemurafenib. In the study, 3 of 12 patients (25%) experienced partial response to treatment (>30% reduction) and 9 (75%) had stable disease (of which 56% had a minor response) to treatment.

As nearly 50% of patients with PTC in the U.S. are BRAFV600E-mutation positive, there remains a need for research into the prognostic implications of the mutation as well as any targeted treatment options.


  1. Brose MS, Cabanillas ME, Cohen EEW, et al. An open-label, multi-center phase 2 study of the BRAF inhibitor vemurafenib in patients with metastatic or unresectable papillary thyroid cancer (ptc) positive for the BRAF V600 mutation and resistant to radioactive iodine. Presented at: European Cancer Congress 2013; September 27-October 1, 2013; Amsterdam, The Netherlands. Abstract LBA28.

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