Initial Management of RR-DTC

Lori Wirth, MD: The initial management of this patient with iodine-refractory PTC [papillary thyroid cancer], tall-cell variant, was active surveillance. It was found basically in her initial work-up and treatment that she had distant metastases that did not take up radioactive iodine, despite the treatment dose of radioactive iodine that she had. The CT [computed tomography] scan of the chest showed a number of small lung nodules. She was entirely asymptomatic. One thing that’s important to know is the pace of the disease. Therefore, she did have a repeat CT scan 3 months later. Active surveillance, so you understand the pace of the disease, is a very reasonable approach for patients that have relatively low burden asymptomatic metastatic disease.

She did, however, have disease progression at that 3-month time interval, and therefore, she was started on lenvatinib. Deciding to proceed with treatments rather than ongoing active surveillance is a judgment call that’s not always easy to make. However, it’s a very important part of the decision-making process for the initial approach to treatment for iodine-refractory disease that’s progressive.

In terms of drugs that are available for these patients in the United States, we have 2 multikinase inhibitors that are approved by the FDA. The first drug that was approved is sorafenib, and that was approved on the basis of the DECISION trial, which was a randomized phase 3 trial comparing sorafenib versus placebo with a primary end point of progression-free survival.

The second drug that was approved is lenvatinib. Lenvatinib was approved on the basis of another randomized phase 3 trial, the SELECT trial, in which patients with iodine-refractory disease that was progressive was in the 14 months prior to study entry were randomized to lenvatinib versus placebo.

In both trials when patients experience disease progression, the randomization was unblinded. Patients who were found to have been on placebo were then offered crossover therapy with sorafenib in the DECISION trial and lenvatinib in the SELECT trial.

How do you decide which to use first? You have 2 FDA-approved drugs. As I mentioned, sorafenib was approved first, and now lenvatinib is also approved. The way I think about this is that we don’t have a head-to-head comparison. I don’t think we’re going to have a head-to-head comparison of the 2 drugs anytime soon. It’s a judgment call. In general, they’re similar drugs. They’re both multikinase inhibitors. They both inhibit the VEGF pathway as well as multiple other kinases. Both drugs have similar adverse-effect profiles that we can talk about a little more.

I can’t use the mechanism of action or the adverse effect profiles so much to make the decision. I look at the activity and efficacy data that we have available from the 2 trials. In the DECISION trial, the overall response rate with sorafenib, in patients who were randomized to sorafenib, was 12%. The progression-free survival in that patient population was 11 months, whereas in the SELECT trial with lenvatinib the overall response rate is 65%, and the progression-free survival on the lenvatinib arm was 18 months.

When I’m comparing apples with oranges with these 2 different phase 3 trials, in general, the data do seem stronger for lenvatinib having a better efficacy. That’s my go-to first drug for most patients with iodine-refractory differentiated thyroid cancer.

Transcript edited for clarity.

Case: A 67-Year-Old Woman With Differentiated Thyroid Cancer

Initial presentation

• A 67-year-old woman presents with a painless “lump on her neck”
• PMH: unremarkable
• PE: palpable, non-tender solitary right-of-the midline neck mass; otherwise unremarkable

Clinical workup

• Labs: including TSH, anti-Tg antibodies WNL
• Ultrasound of the neck revealed a 3.6 cm suspicious right mass arising from the right thyroid; 3 suspicious supraclavicular largest 2.0 cm in size
• Ultrasound-guided FNAB of the thyroid mass and the largest lymph node confirmed papillary thyroid carcinoma
• Patient underwent total thyroidectomy with central compartment and right selective neck dissection
• Pathology: 3.6 cm papillary thyroid cancer arising in right lobe of thyroid, tall-cell features; extrathyroidal extension present; 2 of 6 positive central compartment lymph nodes, largest 1.6 cm, no extra nodal extension; 3 of 13 right lateral compartment involved nodes largest 2 cm, positive extra nodal extension
• StageT2N1MX; ECOG PS 0

Treatment and Follow-Up

• She was treated with radioactive iodine 150 millicuries
  • Whole body scan showed uptake in neck only consistent with thyroid remnant
• Follow-up at 6 months TSH 0.1 mU/L; thyroglobulin 24 ng/mL
• Chest CT scan showed 10 small bilateral lung nodules largest 1.1 cm
• Follow-up CT neck and chest scan at 3 months was notable for a 1-2 mm growth in several lung nodules and 2 new distinct 8 mm lung nodules
• Lenvatinib 24 mg PO qDay was initiated