Cabozantinib Active in RAI-Refractory Thyroid Cancer

Alexander M. Castellino, PhD

February 14, 2018

Cabozantinib (Cabometyx, Exelixis) has shown efficacy in the first-line treatment of radioactive iodine (RAI)–refractory differentiated thyroid carcinoma (DTC) and could offer an option in addition to the drugs approved for this indication, such as sorafenib (Nexavar, Bayer) and lenvatinib (Lenvima, Eisai).

New data from a phase 2 study showed that patients with thyroid cancer that progressed after surgery and RAI achieved an objective response rate of 54% with cabozantinib, and tumor shrinkage was seen in 34 of the 35 enrolled patients.

These data were highlighted at a press conference before their presentation at the 2018 Multidisciplinary Head and Neck Cancers Symposium, to be held in Scottsdale, Arizona, on February 15 to 17.

Presenter Marcia S. Brose, MD, PhD, an associate professor at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, noted that while RAI is curative for most patients, in about 5% to 15% of patients with thyroid cancer, the disease becomes refractory to treatment.

Dr Marcia S. Brose

Patients whose disease is refractory to RAI have the option to be treated with sorafenib or lenvatinib — both vascular endothelial growth factor receptor (VEGFR) inhibitors. She noted, however, that responses to these drugs are not durable and patients need additional therapies. 

"Our positive results indicate that cabozantinib offers an additional option to shrink patients' tumors and provide an additional progression-free period," Brose said.

Cabozantinib is a multikinase tyrosine kinase inhibitors targeting VEGFR, RET, MET, and AXL and is already approved for use in patients with advanced thyroid cancer and renal cell carcinoma.

The manufacturer is exploring other indications. "Based on these promising results and data from other studies of cabozantinib in previously treated DTC, Exelixis plans to initiate a pivotal phase 3 study with cabozantinib in patients with advanced DTC later this year," Gisela Schwab, MD, company president and chief medical officer, said in a statement.

Shows "Good Activity"

Brose presented data from the UPCC 28313 (NCT 02041260)  study, which enrolled 35 patients with metastatic, RAI-refractory thyroid cancer who had not received prior treatment with VEGFR inhibitors. Median age at enrollment was 65 years, and three fourths of the patients had papillary thyroid cancer.

Patients received cabozantinib, 60 mg daily.

The study was powered to detect an overall response rate of 15%, which translates to responses in at least 5 of the 35 patients.

Although no patient showed a complete response, partial responses were seen in 19 of 35 (54%) patients and stable disease was reported for 15 of 35 (43%) patients. Duration of partial response ranged from 11 weeks to more than 174 weeks.

Stable disease lasting for greater than 6 months was seen in 9 of 35 (26%) patients and ranged from 8 weeks to more than 142 weeks.

The clinical benefit rate (complete response + partial response + stable disease for >6 months) was reported for 80% of patients.

Brose reported that only 6 patients had disease progression so far and that median progression-free survival was not reached. Median time on drug was 35 weeks, and as of last week 16 patients were still receiving study treatment. Although the treatment was well tolerated, 23 patients required dose interruptions.  

Most common adverse events were hyperglycemia (80%), diarrhea (77%), malaise/fatigue (74%), and weight loss (71%). Grade 3/4 adverse events occurring in more than one patient were hypertension (14%), increased lipase (9%), pulmonary embolism (6%), and hyponatremia (6%).

Brose noted that the two approved drugs in the setting of RAI-refractory thyroid cancer are used sequentially. "But patients ultimately progress and need more treatment options," she said. "Cabozantinib will provide relief for these patients," she added.

Danielle Margalit, MD, a radiation oncologist at the Dana-Farber Cancer Center, Boston, Massachusetts, who moderated the presscast, remarked that these results are highly significant. "Cabozantinib has good activity in these patients and its activity is comparable to recently approved agents," she said.

However, she said that cabozantinib will need to be further evaluated in phase 3 studies and that the design of such a study is underway. When questioned about whether the drug is available to patients, Brose responded that once these data are published, there is hope that reimbursement will not be an issue. However, the best way to access the drug now is through a phase 3 trial, she indicated.

When the drug becomes available, Brose said that three good drugs will be available to patients in the first-line setting. "There is an art to sequence these drugs," Brose told Medscape Medical News. For example, with the current options, patients aged 65 years and older are prescribed lenvatinib because of favorable survival data in this population. Lenvatinib may also be prescribed for patients who need a quick response. For patients with indolent disease, sorafenib and lenvatinib are both viable options.

"With the availability of all these options, it does not matter which drug is used first," Brose said. "What is important is that patients have options. Over 90% of patients have good performance status even after two therapies, and a third one will fill a high unmet need," she said.   

The study was funded by Elixir Pharmaceuticals, the maker of cabozantinib. The trial was initiated and led by the Abramson Cancer Center at the University of Pennsylvania.  Brose receives grant funding from Loxo, Elixis, Bayer, Eisai, Genzyme/Sanofi, and AstraZeneca. She has also received honoraria or consulting fees from Loxo, Bayer, Eisai, Genzyme/Sanofi, and Blueprint pharmaceuticals

2018 Multidisciplinary Head and Neck Cancers Symposium. Abstract 8. To be presented February 16, 2018.

Follow Medscape Oncology on Twitter: @MedscapeOnc

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....