Recommendations for Treatment of RR-DTC

Lori Wirth, MD: One of the challenges in managing patients with iodine-refractory DTC [differentiated thyroid cancer] is deciding when to start therapy with a drug like lenvatinib. How long is it OK to follow patients without starting therapy and follow them with active surveillance?

We have some data now from subsequent analyses of the SELECT trial that can help get at that important question. What we’ve done is we’ve looked at how patients do when they have an ECOG performance status of 0 versus 1. We know because of eligibility criteria that patients otherwise were relatively healthy. Most of the patients who had an ECOG performance status of 1 probably did have a performance status of 1 because of symptoms from their thyroid cancer.

What we found in this analysis is that outcomes are better in patients with an ECOG performance status of 0 versus 1. I don’t think the right answer is to not start any therapy until the patients develop symptoms from their disease, because then the benefit of therapy is not as good as if we’d start earlier in the disease process.

We also took a look at whether patients have more benefit or less benefit, if they have more disease or less disease. For example, if patients have larger tumor burdens with a larger sum of the longest diameters of the lesions, do they have a better response to lenvatinib or not? What we actually found is the opposite, that when patients have less disease they have better responses that last for a longer period of time, again suggesting that we don’t necessarily want to wait as long as possible before starting lenvatinib if we want to get the most therapeutic benefit from lenvatinib.

Lastly, we took a look at that question in a way by looking at how patients do with lung metastases. What we found was that when patients have lung metastases—even when they’re relatively small, just greater than 1 cm—that when they were randomized to lenvatinib versus placebo, there was actually an overall survival benefit for patients with lung metastases as small as 1 cm in size. That overall survival benefit, even though there was crossover from placebo to lenvatinib at the time of progression, to me it means patients can do very well with lenvatinib even when they have a relatively low burden of disease when it’s progressive.

I think about all of those things when I’m trying to make that difficult decision of advising the patient when to move from active surveillance to active treatment.

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