Impact of Drug, Genomic Innovations on Thyroid Cancer Treatment
There were no effective therapeutic options for advanced thyroid cancer until 5 years ago.
CHICAGO — There were no effective therapeutic options for advanced thyroid cancer until 5 years ago, a presenter said at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.
"Our understanding of the molecular basis of thyroid carcinogenesis improved, and clinical trials developed based on in vitro data demonstrated that kinase inhibitors interfered with thyroid cancer cell growth," Ann W. Gramza, MD, medical oncologist at the MedStar Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, explained during a poster discussion session.
There are 4 kinase inhibitors approved by the U.S. Food and Drug Administration for thyroid cancer: lenvatinib and sorafenib for differentiated thyroid cancer, and vandetanib and cabozantinib for medullary thyroid cancer. All target the vascular endothelial growth factor receptor (VEGFR).
During her presentation, Dr Gramza discussed 2 studies of novel kinase inhibitors, anlotinib and cediranib, for the treatment of medullary thyroid carcinoma and differentiated thyroid cancer, respectively.1
The activity and tolerability of anlotinib was evaluated in a phase 2 study that included 58 patients with medullary thyroid cancer from 8 centers in China. Anlotinib was administered at a dose of 12 mg orally daily for 2 weeks on and 1 week off. The median progression-free survival has not yet been reached and the 48-week disease control rate was 84.5%.2
In her discussion of the results, Dr Gramza said that compared with vandetanib, the objective response rate was similar (48% with anlotinib vs 45% with vandetanib), but grade 3 or worse diarrhea and hypertension were less frequently reported with anlotinib.1 She also reported that compared with cabozantinib, anlotinib was associated with a higher response rate (48% vs 28%); however, the studies should not be compared as patients in the cabozantinib study were required to have RECIST progression prior to enrollment, unlike the anlotinib trial.1 In terms of safety, anlotinib resulted in fewer reports of hand-foot syndrome vs cabozantinib,1 she noted.
"Anlotinib was associated with a good response rate compared to historical controls with manageable toxicity profile," Dr Gramza said. "However, it is unclear if the drug will be available outside of China."
The other study evaluated cediranib alone or with lenalidomide in iodine-131-refractory patients with differentiated thyroid cancer. That phase 2 trial demonstrated that the addition of lenalidomide was not beneficial; however, cediranib was associated with an objective response rate of 44% and a median progression-free survival of 14 months.3 For comparison, sorafenib and lenvatinib yielded objective response rates of 12% and 65%, respectively, and median progression-free survival of 10.8 months and 18.3 months,1 respectively, according to Dr Gramza.
"This was a negative trial; more is not always better," she explained. "Although cediranib alone has encouraging results in differentiated thyroid cancer, it is unclear as to whether there will be further cediranib trials in differentiated thyroid cancer or other histologies."
Dr Gramza then discussed a comprehensive genomic profiling study of 90 patient samples of anaplastic thyroid cancer, which is the largest sample size of an anaplastic thyroid cancer molecular analysis to date.4
"Anaplastic thyroid cancer is extremely rare and aggressive," Dr Gramza noted. "There are no effective chemotherapy options and it has a higher mutational burden than differentiated thyroid cancers."
The study identified TP53, BRAF, CDKN2A, TERT, and NRAS as the most common gene mutations in the 90 patients, which is similar to what previous research has demonstrated.4
"What are the potential benefits of prospective analyses?" Dr Gramza asked. "Identify genomic abnormalities driving tumorigenesis; identify potential clinical trials and/or potentially effective therapies that target the molecular abnormality; identify molecular factors that predict prognosis; and identify molecular factors that predict response and resistance to therapy."
"Moving forward, we need to better understand mechanisms of carcinogenesis and define targets, develop drugs that are unique or superior in some way to those already available, and discover mechanisms of response and resistance to design rational combination trials," Dr Garza concluded.
It is also unclear how immunotherapy will impact the treatment landscape of thyroid cancer, as it has substantially improved outcomes for patients with other cancer types.
- Gramza AW. Thyroid cancer innovations. Presented at: 2016 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2016; Chicago, IL.
- Sun Y, Chi Y, Tang P, et al. Phase II study of anlotinib for treatment of advanced medullary thyroid carcinoma. J Clin Oncol. 2016; 34 (suppl; abstr 6015).
- De Souza JA, Karrison T, Libao B, et al. Randomized phase 2 trial of cediranib alone or cediranib plus lenalidomide in iodine 131-refractory differentiated thyroid cancer (DTC): A University of Chicago Phase 2 Consortium trial. J Clin Oncol. 2016; 34 (suppl; abstr 6013).
- Khan SA, Ci B, Gerber DE, et al. Comprehensive genomic sequencing (CGS) of 90 patient samples of anaplastic thyroid cancer (ATC). J Clin Oncol. 2016; 34 (suppl; abstr 6014).