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Zelboraf linked to antitumor activity in BRAF-mutated papillary thyroid cancer
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Vemurafenib was associated with antitumor activity in treatment-naive and tyrosine kinase inhibitor-pretreated patients with radioactive iodine refractory, progressive, BRAF V600E-mutated papillary thyroid cancer, according to phase 2 study results presented at the European Cancer Congress.
In a phase 1 trial, vemurafenib (Zelboraf, Hoffmann-La Roche) demonstrated response or stable disease in three patients with BRAF V600E-mutated papillary thyroid cancer.
Marcia S. Brose
“In this phase 2 study, we took the BRAF V600E inhibitor vemurafenib and studied it in BRAF-mutated papillary thyroid cancer patients to see if there’s an effect,” Marcia S. Brose, MD, PhD, director of the thyroid cancer therapeutics program and assistant professor of otorhinolaryngology at the Abramson Cancer Center and Perelman School of Medicine at the University of Pennsylvania, said in a press release.
Brose and colleagues examined data from 51 patients (21 TKI treatment-naive and 25 pretreated patients) who harbored BRAF V600E mutations and were enrolled at 10 centers worldwide between June 2011 and January 2013.
All of the patients had ECOG performance status of 0 or 1 and had either received prior surgery or radioactive iodine (RAI) treatment. Fifty-three percent were aged ≥65 years.
Three (12%) patients in the TKI treatment-naive cohort and seven (28%) patients in the pretreated cohort had previously received chemotherapy, and 21 (84%) pretreated patients also had received prior sorafenib (Nexavar, Bayer).
Patients in both cohorts received vemurafenib 960 mg orally twice daily and were examined for tumor response after every 8 weeks of treatment.
Best overall response rate as indicated by RECIST criteria in the treatment-naive arm served as the primary endpoint. Best overall response rate in the pretreated arm, as well as PFS and OS in both treatment arms, served as secondary endpoints.
At the preplanned primary endpoint analysis, 6 months after enrollment of the last patient, the researchers observed that best overall response rates was 35% for TKI treatment-naive patients and 26% for pretreated patients. Researchers observed no complete response. All best overall response rates were partial response.
The clinical benefit rate — defined as complete response plus partial response plus stable disease for at least 6 months — was 58% for the TKI treatment-naive cohort and 36% for pretreated patients.
Median PFS at the time of data cutoff for the analysis was 15.6 months in the TKI treatment-naive cohort and 6.8 months in the pretreated patients. Seven patients in TKI treatment-naive cohort and 11 pretreated patients discontinued treatment due to progressive disease.
“Our results show that we can effectively treat [papillary thyroid cancer] patients that have progressive disease by targeting a common mutation, and produce clinically meaningful periods of progression-free survival,” Brose said.
Overall toxicity profile was consistent with that observed with vemurafenib treatment among melanoma patients, with notable exceptions of higher rates of weight loss, dysgeusia, anemia, increased creatinine and liver laboratory abnormalities. Common adverse events included increased bilirubin, rash, fatigue and weight loss.
“A few years ago, there was nothing to offer these patients,” Brose said. “By understanding similarities across different types of cancers, we have been able to show that therapies previously shown to be effective in other cancers, such as liver, kidney and bone, can be effectively used to treat a rare cancer, providing significant hope to these patients.”
For more information:
Brose MS. Late Breaker #28. Presented at: The European Cancer Congress 2013; Sept. 27-Oct. 2, 2013; Amsterdam.
Disclosure: The researchers report funding from Hoffmann-La Roche.