BACKGROUND

Most patients with thyroid cancer respond to the standard treatment consisting of surgery followed by radioactive iodine therapy and have excellent results, with 10 year survival rates in the 95+% range. However, 3–5% of thyroid cancer patients have progressive cancer after the initial treatment, requiring alternative therapies. Until recently, there was little to offer these patients in terms of chemotherapy. However, 2 chemotherapy drugs from the tyrosine kinase inhibitor (TKI) group, sorafenib and lenvatinib, have been shown to delay the cancer progression and have been approved to be used for patients with persistent and progressive thyroid cancer not responding to radioactive iodine therapy. The TKI therapy is promising, despite many significant side effects. Importantly, patients taking lenvatinib appear to have a lower risk to develop resistance to treatment as compared to sorafenib. Therefore, this medication may remain effective for a prolonged period.

Lenvatinib was approved based on the results of the SELECT clinical trial, which showed that this medication stopped the cancer progression for a longer time as compared to no drug (18 vs. 4 months). Additional data was collected in the SELECT study over the next three years of follow-up to update the initial analysis of the effect of lenvatinib. The aim of this study was to evaluate the duration of response to lenvatinib, which is defined as the time from when the cancer responded to treatment to when the disease started to progress again.

THE FULL ARTICLE TITLE:

Gianoukakis AG et al 2018 Prolonged duration of response in lenvatinib responders with thyroid cancer. Endocr Relat Cancer 6:699–704. PMID: 29752332

SUMMARY OF THE STUDY

The SELECT study included 392 patients with thyroid cancer not responding to radioactive iodine therapy and progressing within the previous 13 months. Patients were randomly assigned 2:1 to receive 24 mg of oral lenvatinib daily (261 patients) or no drug (placebo, 131 patients) until the cancer started to progress, the patients developed an unacceptable toxicity to the treatment, or the patients withdrew from the study. The data collected prior to November 15, 2013 was used for the initial analysis. After this, the patients in the placebo group who had progressive cancer could choose to receive lenvatinib treatment.

Additional data collected over the next three years until September 1, 2016 was used for the current study. A total of 157 patients (60%) had a complete or partial response to the levantinib treatment. The patients who responded to lenvatinib had stable disease for an average of 30 months. The duration of the response to treatment appeared to be shorter in patients with large cancer and for patients with spread of the cancer to the liver or brain. The duration of the response to treatment was similar for patients who had received one prior cancer therapy and those who had never received therapy prior to the study. A total of 80% of lenvatinib-treated patients experienced serious treatment-related adverse events, most of them occurring early in the course of treatment.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?

This updated analysis confirmed that lenvatinib can delay the progression of thyroid cancer in patients not responding to radioactive iodine therapy and further showed that the patients who responded to lenvatinib could have a prolonged, durable effect, lasting for approximately 30 months. More than half of patients may respond to this treatment. Since most patients experienced side effects from the levantinib, early recognition and adequate treatment of the side effects is especially important to allow treatment continuation.

— Alina Gavrila, MD, MMSC

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