Second-Line Treatment Options
An expert briefly discusses the second-line treatment options for patients with DTC that have progressed on first-line therapy.
Marcia S. Brose, MD, PhD: With the FDA approval of sorafenib [Nexavar] and lenvatinib [Lenvima], we eventually developed a large class of patients who had progressed on either sorafenib or lenvatinib. Then the question comes: what do you do next? There were data from the original SELECT trial that showed that lenvatinib is active after sorafenib. For most of the patients who had gotten a prior multikinase inhibitor, that was the multikinase inhibitor they had received. But most of our patients at this time are started on lenvatinib in the first-line therapy. Recently data that were presented at ASCO [American Society of Clinical Oncology Annual Meeting] in 2021 and subsequently published show that cabozantinib [Cabometyx] is also active in this case. It has been FDA approved in the second line.
Patients may be on lenvatinib for years, but at the time they start to escape the lenvatinib blockade, we find that patients have very aggressive disease. If they don’t have any molecular markers, the best option is cabozantinib. If they do have molecular markers, people will question whether they should be targeting them.
In the case of TRK and RET inhibitors, if they have not had that, I would do that first, right away, because those agents are well tolerated and very effective. They have efficacy rates of 60% to over 70%. I don’t recommend using a BRAF inhibitor before lenvatinib because lenvatinib has a response rate in the 60% range. For BRAF inhibitors, whether it’s vemurafenib or dabrafenib, response rates are more like 20% to over 30%. It has half the response rate.
I don’t feel that with good monitoring, the AE [adverse event] profile is that much superior to justify giving an inferior drug as far as response goes. Our patients are usually started on lenvatinib, and then they would have cabozantinib as an option. Of course, molecularly targeted therapies are always an option. If a patient can’t tolerate a VEGF multikinase inhibitor and they have a BRAF mutation, then certainly we’d try them on vemurafenib [Zelboraf] or dabrafenib [Tafinlar].
This transcript has been edited for clarity.
Case: A 70-Year-Old Woman With Differentiated Thyroid Cancer
Initial presentation
- A 70-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 and initial treatment
- Labs: TSH WNL
- Ultrasound of the neck revealed a 3.4 cm suspicious right mass arising from the right thyroid; 4 suspicious supraclavicular lymph nodes (LNs), largest 2.2 cm in size.
- Ultrasound-guided FNAB of the thyroid mass and the largest LN confirmed papillary thyroid carcinoma.
- Patient underwent total thyroidectomy with central compartment and right selective neck dissection.
- Pathology: 3.4 cm papillary thyroid cancer arising in the right lobe of thyroid, tall-cell features; extrathyroidal extension present;
- 2 of 6 positive central compartment lymph nodes, largest 1.8 cm
- 4 of 13 right lateral compartment involved nodes largest 2.2 cm in size, positive extra nodal extension.
- StageT2N1aMX; ECOG PS 0
Subsequent treatment and follow-up - She was treated with radioactive iodine 150 millicuries
- Whole body scan showed uptake in the neck, consistent with thyroid remnant but no uptake in the lungs
- Follow-up at 3 months
- TSH 0.2 µU/mL, thyroglobulin 28 ng/mL (negative anti-thyroglobulin antibodies)
- Chest CT scan showed 8 small bilateral lung nodules largest 1.3 cm
- Follow-up CT neck and chest scan 3 months later was notable for 1-2mm growth in several lung nodules and 3 new distinct 9.5 mm lung nodules
- Next-generation sequencing was negative for mutations, rearrangements
- Lenvatinib 24mg po qd was initiated
Case 2: A 57 Year-Old Man With Differentiated Thyroid Cancer
Initial presentation
- A 57-year-old man presents with a solitary nodule on the neck and occasional shortness of breath and intermittent excessive fatigue
- PMH: unremarkable
- PE: palpable, hard and fixed solitary nodule in the anterior neck
Clinical workup and initial treatment
- Labs: TSH 10.3 µU/mL; all others WNL
- Ultrasound of the neck revealed a 2 cm mass near the isthmus of the thyroid; several suspicious lymph nodes ranging from 0.3-2.4 cm in size
- Ultrasound-guided FNAB: confirmed papillary thyroid carcinoma; with nuclear enlargement and nuclear grooves, no colloid seen
- Patient underwent total thyroidectomy with bilateral central neck dissection
- Pathology: 2.1 cm papillary thyroid cancer arising in isthmus of the thyroid, 3 of 7 positive central compartment lymph nodes, largest 1.8 cm, positive extra nodal extension
- StageT2N1MX; ECOG PS 1
Subsequent treatment and follow-up
- He was treated with radioactive iodine 150 millicuries
- Whole body scan showed uptake in the neck; indicative of thyroid remnant
- Follow-up at 3 months TSH 0.2 µU/mL, thyroglobulin 68 ng/mL
- Neck US showed no evidence of residual disease in thyroid bed, no suspicious neck nodes. Chest CT was done: 4 lung lesions that were 0.3 and 0.6 cm in size
- The physician recommended not initiating systemic therapy and putting the patient on active surveillance
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