Patient Profile 1: Radioiodine-Refractory Differentiated Thyroid Cancer

Expert Marcia Brose, MD, details a clinical scenario wherein a patient is diagnosed with differentiated thyroid cancer and managed with surgical and radiotherapy.


Marcia Brose, MD: Welcome and thank you for joining me. Today we're going to discuss recent advances in the treatment of differentiated thyroid cancer and their impact on clinical practice. We will present 2 real-world patient cases and discuss their treatment approach to illustrate how we incorporate recent data in our practice. Let's get started on the first topic. Patient profile number 1. I'll present a case and talk about the data that informed decision-making as far as treatment planning. And then in the second patient profile, Dr Wirth will share her case as well, and we'll discuss that afterwards.

To start with, this patient with the initials J.C., is a 56-year-old [man who was] originally diagnosed in January 2010, when he underwent a total thyroidectomy at a community hospital. Pathology showed a 4-cm papillary thyroid cancer with tall cells histology. He was found to have positive margins and lymphovascular invasion, and papillary thyroid cancer was also identified in 5 adjacent lymph nodes. In May, he was treated with RDI [recommended dietary intake] and received a 124 millicuries. But unfortunately, on further review at the time, [it was] revealed that he had not been on a low iodine diet.

I'm joined today by my 2 experts in the field of thyroid cancer, and I'd like to ask my esteemed colleagues to introduce themselves. Dr Wirth?

Lori Wirth, MD: Hi, good afternoon. I'm Lori Wirth. I'm the medical director of head and neck oncology at Massachusetts General Hospital in Boston, and an associate professor of medicine at Harvard Medical School.

Marcia Brose, MD: And Dr Robinson?

Bruce Robinson, MD: I'm Bruce Robinson. I'm an endocrinologist at the Royal North Shore Hospital in the University of Sydney, and a professor of medicine at the University of Sydney.

Marcia Brose, MD: In September 2010, he had a recurrence detected in a supraclavicular lymph node which was biopsied and revealed papillary thyroid cancer. He went back to the OR [operating room] for bilateral selective neck lymph node dissection, and multiple lymph nodes were found; all of them, or many of them, were affected. He underwent another dissection in August, and in November he was given a low dose of radioactive iodine on a whole-body scan, which was negative for any uptake, and no treatment was given. A few days later, he had a PET [positron emission tomography]-CT, which revealed FDG [fluorodeoxyglucose]-positive lymph nodes in the neck and sternocleidomastoid muscle, indicative of RAI [radioactive iodine] non-avid disease, but interestingly, there was no disease outside of the neck. He had another bilateral neck dissection in February, and in May of 2013, he underwent surgery again, where multiple lymph nodes on both sides again that were affected were removed. Still, no disease was found in his chest. In July of 2013, he moved his care to Penn, where he was followed by EMT and underwent a CAT scan, which showed the lymph nodes in the superior mediastinum and paratracheal areas. But he's also found to have now a 4-millimeter middle lobe lesion. However, his disease was still slowly growing, and he was followed expectedly until May of 2015, but he went once more to the OR for right neck dissection for additional sites of metastatic disease, and 1 out of 7 lymph nodes was found to be positive. In June of 2015, he had external beam radiation to the neck since most of his disease was in the neck. But following that, no more radioactive iodine or extra external beam treatment was given. In May of 2019, he was found, however, to have significant progression on an ultrasound of the upper mediastinum and this was also followed by CT of the neck, which revealed significant interval enlargement of his thoracic lymph nodes and neck lymph nodes. This was followed by CT of the neck and chest, which revealed significant interval enlargement of his thoracic nodules and lymph nodes. A particular concern were the bulky hilar lymph nodes ranging from 2 to 4 cm. He was referred to medical oncology, as part of his work-up, RNA-based next-generation sequencing was attempted on the lymph nodes removed in 2015, which were his most recent. But the quantity was not sufficient, so DNA, NGS [next-generation sequencing] was completed instead, and he was found to harbor a BRAF V600E mutation and a PI3- kinase mutation as well. When we reviewed at the time the options for treating him, there were 2 agents that have been FDA [United States Food and Drug Administration]-approved based on large international phase 3 studies, the decisions that had led to the FDA approval of sorafenib. What we see is that the overall response rate in the study for strapping it was 12%, about a year later, the Selleck study was completed with afatinib and that response rate was 63% with an additional 2% that were considered complete responses; the duration of responses are shown also in the bottom. At the time, we had a choice, mostly between sorafenib and lenvatinib. However, also at the time, we had results of a phase 2 study, which was for vemurafenib. And vemurafenib, was shown only in a small cohort of about 626 patients to also have activity with a partial response of 38%. Now keep in mind, this is phase 2, this was not a large phase 3 study and this agent was not FDA approved. We have the option of treating with either lenvatinib, sorafenib or vemurafenib at that point. In summary, JC is a 56-year-old man with a diagnosis of metastatic papillary thyroid cancer, now metastatic to the lungs and progressing. He had a CPD [Center for Personalized Diagnostics] solid tumor panel which showed BRAF mutation and a PI3-kinase mutation, and on July 6 of 2019, he was started on lenvatinib, 24 mg a day. He was started on 24 mg a day because at that time that was the starting dose that we used in the clinical trials, and lenvatinib was chosen over sorafenib because of its improved response rate of 63% compared to 12%. It was also chosen instead of vemurafenib because it was felt that the adverse effect profile was not that different, but the response rate was double, and it also had been shown in a large international phase 3 trial, and the safety data was what was very well known at the time.

Transcript edited for clarity.

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