Sequential Combination Strategy May Be Optimal in Advanced Thyroid Cancer

It may be best to simply begin with the mTor inhibitor everolimus and add the somatostatin analogue pasireotide later in patients with advanced thyroid cancer, according to a new study presented at the 86th Annual Meeting of the American Thyroid Association (ATA). Researchers from Emory University reported that this sequential combination strategy may offer improved tolerability and efficacy over an immediate combination strategy.

“The sequential combination of mTOR inhibitor with somatostatin analogue pasireotide is a promising treatment strategy for patients with advanced-stage thyroid cancer. This is the first study of its kind to prospectively test this strategy in thyroid cancer,” said study investigator Taofeek Owonikoko, MD, PhD, associate professor and associate vice chair for faculty development and translational research in the department of hematology/oncology at Emory University, Atlanta, Georgia.

Dr Owonikoko and colleagues looked for evidence of efficacy for the 2 anticancer agents when given alone and when given in combination. They also tested whether the order in which the 2 drugs are combined impacts the overall benefit that patients obtain. They observed that the 2 drugs, particularly everolimus, are able to control the growth of thyroid cancer in patients.

“We also found that giving the 2 drugs together right from the start of treatment did not appear to lead to greater efficacy. However, patients who first received everolimus alone and later received the combination of pasireotide and everolimus after everolimus by itself had the longest duration of benefit. We therefore conclude that this strategy would be the best strategy to test in this patient population going forward,” Dr Owonikoko told Endocrinology Advisor.

Dr Owonikoko presented data on 42 adult patients with differentiated and medullary thyroid cancer. All the patients had progressive medullary thyroid cancer and iodine-refractory differentiated thyroid cancer previously untreated or treated with 1 systemic therapy. Patients were randomly assigned to receive everolimus, pasireotide, or the combination of both drugs.  At progression, patients in the everolimus arm or pasireotide arm were switched to the combination of both agents. Treatment continued until progression or intolerable toxicity.

For this study (ClinicalTrials.gov identifier: NCT01270321), the primary end points included response rate (RR) and 1-year progression-free survival. Interim analysis was conducted after enrolling 34 patients. However, a final analysis was conducted after enrolling 42 patients, of whom 32 had differentiated thyroid cancer and 10 had medullary thyroid cancer (mean age, 64 years). They were randomly assigned to everolimus (n=19), pasireotide (n=11), and combination (n=12).

The most frequent adverse events were thrombocytopenia, anemia, stomatitis, fatigue, hyperglycemia, and hypercholesterolemia. Dr Owonikoko said there was no objective response by RECIST criteria across the 3 arms of the study.

The 1-year progression-free survival rate was 49.9% for the everolimus arm, 36.4% for the pasireotide arm, and 25% for the combination arm. The median progression-free survival after patients received both agents was 26.3 months for patients starting with everolimus arm and later receiving the combination of both. It was 17.5 months for the pasireotide arm and 8.1 months for patients who started with the combination of both agents. Median overall survival was 41.6% for the everolimus arm, 39.4% for the pasireotide arm, and 24.3% for the combination arm.

There were no noticeable differences in terms of efficacy by histology and gender. 

“Our findings that the sequence in which drugs are administered matters would be very useful as more and more drugs get approval from the Food and Drug Administration for the treatment of advanced stage thyroid cancer,” said Dr Owonikoko.

Disclosures: Dr Owonikoko reports receiving grants/research support from Novartis, Bayer, and AstraZeneca, and serving as a consultant for Novartis and Onyx.

For more coverage of ATA 2016, click here.

Reference

1. Owonikoko TK, Julie B, Chen Z, et al. Short Call Oral Abstract 8. A 3-arm multicenter randomized phase II study of single agent, immediate and delayed combination of everolimus and pasireotide LAR in advanced thyroid cancer. Presented at: American Thyroid Association Annual Meeting; September 21-25, 2016; Denver, Colorado.