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Thyroglobulin level, prior therapy do not predict pazopanib response in differentiated thyroid cancer
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LAKE BUENA VISTA, Fla. — Pazopanib exhibited significant clinical activity in patients with progressive, radioactive iodine-refractory differentiated thyroid cancer, according to phase 2 study results presented at the International Thyroid Congress.
However, associated changes in serum thyroglobulin (Tg), tumor mutational status and prior therapy receipt did not act as predictive factors for treatment response, according to Keith C. Bible, MD, PhD, professor of oncology at Mayo Clinic in Rochester, Minnesota.
Keith C. Bible
“In other tumors, we find that induced changes to tumor markers do not always forecast response,” Bible told HemOnc Today. “Sometimes, they can paradoxically increase rather than decrease, as we sometimes see with ovarian cancer.”
Tyrosine kinase inhibitors have exhibited disease-modifying activity in patients with advanced, radioactive iodine-refractory (RAIR) differentiated thyroid cancer, according to study background.
Bible and colleagues sought to observe the clinical effects of the TKI pazopanib (Votrient, Novartis) in patients with progressive RAIR differentiated thyroid cancer. Further, they conducted a parallel assessment of potential correlations between therapy response and changes in Tg.
Researchers conducted a one-stage phase 2 trial composed of 60 patients, 91.7% of whom had previously received systemic therapy in addition to radioiodine. Patients remained on treatment for a median of 10 cycles (range, 1-53+).
Adverse events observed were consistent with previous reports. The most common grade 3 or higher adverse events included hypertension (23%), fatigue (8%), decreased neutrophil count (8%), diarrhea (7%) and hand–foot disease (7%).
Fifty-three percent of patients who experienced severe hypertension required therapeutic changes.
However, the researchers attributed no deaths to the study drug.
Twenty-two patients (36.7%; 95% CI, 24.6-50.1) achieved partial response confirmed by RECIST criteria.
Although Tg change after the first cycle (4 weeks) did not differ by response, a greater Tg nadir occurred among 20 patients who achieved partial response (median, –86.8%; 95% CI, interquartile range [IQR], –90.7 to –70.9) compared with 28 patients who maintained disease stability at best (median, –69%; 95% CI, IQR –78.1 to –27.7).
BRAF, p53, JAK3 and/or HRAS mutations occurred in 11 of 16 patients evaluated for mutations; however, the researchers did not find correlations between mutation status and disease response.
Further, prior therapy receipt did not correlate with response to pazopanib.
“We had hoped that there might be a way to parse patients early on,” Bible said. “However, that seems not to be the case with Tg. That might come as a surprise to endocrinologists, but in medical oncology, it is something we see frequently.” – by Cameron Kelsall
For more information:
Keith C. Bible, MD, PhD, can be reached at Mayo Clinic, 200 First St. SW, Rochester, MN 55901; email: bible.keith@mayo.edu.
Reference:
Bible KC, et al. Short Oral Communication 103. Presented at: International Thyroid Congress; Oct. 18-23, 2015; Lake Buena Vista, Fla.
Disclosure: The researchers report no relevant financial disclosures.