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Cabozantinib safe, effective in advanced, refractory differentiated thyroid cancer
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LAKE BUENA VISTA, Fla. — Cabozantinib demonstrated significant activity in patients with differentiated thyroid cancer who progressed following treatment with VEGF receptor-targeted therapies, according to phase 2 study results presented at the International Thyroid Conference.
The oral multikinase inhibitors (MKI) sorafenib (Nexavar, Bayer Healthcare) and lenvatinib (Lenvima, Eisai) — which target VEGF receptors (VEGFR) — are currently approved as first-line therapies for patients with radioiodine-refractory advanced differentiated thyroid cancer, according to study background.
“The standard of care over the decades for differentiated thyroid cancer has been surgery, radioiodine [RAI] therapy and external beam radiotherapy,” Manisha H. Shah, MBBS, MD, professor of internal medicine and director of the neuroendocrine tumor clinic program at The Ohio State University Wexner Medical Center, said during a presentation. “Over the last decade, many researchers have worked on tyrosine kinase inhibitor therapies and we now have two drugs that are approved as first-line treatment for progressive thyroid cancer. However, there is a need for second-line therapy.”
Cabozantinib (Cometriq, Exelixis) — an oral MKI that targets MET and VEGFR — is currently indicated for the treatment of medullary thyroid cancer.
In a phase 1 study of eight patients with differentiated thyroid cancer, five patients with one prior MKI treatment achieved an objective response with cabozantinib.
Shah and colleagues conducted a multicenter phase 2 trial of RAI-refractory patients with differentiated thyroid cancer who had measurable disease after one or two prior VEGFR-targeted therapies. The researchers assigned patients to a starting dose of cabozantinib at 60 mg per day, with the option to escalate to 80 mg if the patient failed to achieve a response.
Tumor assessments were conducted every 8 weeks.
The study included data from 25 patients (median age, 64 years; 64% men). Twenty patients had one prior therapy line; the remaining five patients had two prior lines. Sorafenib and pazopanib (Votrient, Novartis) served as the most common prior VEGFR-targeted therapies.
The most common grade 3 adverse events included fatigue (8%; n = 2), hand–foot skin reactions (8%; n = 2), diarrhea (8%; n = 2) and weight loss (4%; n = 1).
Nine patients remained on a 60-mg dose of cabozantinib, whereas four patients escalated their daily dose.
Five patients discontinued treatment definitively due to adverse events. Further, an additional five patients required a dose reduction to 40 mg per day.
“There were lots of individualized treatment options taken,” Shah said. “Clearly, one size does not fit all.”
Nine patients (36%; 95% CI, 18-57) had a confirmed partial response and 12 patients (52%) achieved stable disease. One patient had progressive disease as best response to therapy. Two patients had unconfirmed partial response.
The median PFS rate was 12.8 months. Median OS had not been reached at time of reporting.
“Cabozantinib is a well-tolerated MKI for second- or third-line treatment,” Shah said. “It is effective in inducing partial remission and providing statistically and clinically significant activity.” – by Cameron Kelsall
Reference:
Shah MH, et al. Oral Abstract 73. Presented at: International Thyroid Conference; Oct. 18-23, 2015; Lake Buena Vista, Fla.
Disclosure: Shah reports a leadership role with the International Thyroid Oncology Group, as well as advisory roles with Eisai and Exelixis. HemOnc Today was unable to obtain a list of the other researchers’ relevant financial disclosures at the time of reporting.