Treatment choices in thyroid cancer

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Published: 10 Sep 2017
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Prof Makoto Tahara - National Cancer Center Hospital East, Kashiwanoha, Japan

Prof Tahara talks with ecancer at the ESMO 2017 Congress in Madrid about existing treatments of thyroid cancer, including radioactive iodine treatment and surgery.

He notes the clinical activity of some cytotoxic drugs in treating thyroid cancer, but that sorafenib and lenvatinib offer significant improvement of progression free survival with a better toxicity profile, leading to approval. 

Prof Tahara details the comparative success of lenvatinib as a potential treatment choice for radio-iodine resistant thyroid cancer, based on results from the SELECT trial, describing associated toxicity as manageable, and that PFS in this trial favoured shorter durations of drug interaction.

This programme has been supported by an unrestricted educational grant from Eisai.

 

Professor Makoto, thank you for talking to ecancer. Tell us about yourself.

I am a medical oncologist from the National Cancer Center Hospital East, Japan. My speciality is head and neck medical oncology. I’ve taken charge of treatment of head and neck cancer for more than twenty years.

And one of the cancers you have to look after is thyroid cancer and the common treatment for that is radio iodine.

Yes, but [?? 0:35] treatment for different sorts of cancer is surgery and subsequently they receive radioactive iodine therapy as a [?? 0:47] operation or as adjuvant treatment according to the risk of recurrence.

We know, of course, that some of the thyroid carcinomas are resistant to radio iodine.

That’s right.

So what do you do in your clinic in Japan in that situation?

As you know, a number of cytotoxic drugs have been investigated. Several cytotoxic drugs demonstrated clinical activity but limited response duration and considerable toxicity. Therefore patients with radioactive iodine refractory DTC until approval of a VEGFR targeted TKI have really presented an unmet clinical need. But recently VEGFR targeted TKIs, including sorafenib, lenvatinib, have demonstrated a significant improvement in progression free survival over placebo, leading to approval for this population. So now we can use these two drugs for this population.

Tell me about those two drugs.

Lenvatinib demonstrated significant improvement in progression free survival over placebo with a hazard ratio of 0.21 and it extended median progression free survival by 14.7 months compared to placebo. That’s a great benefit for patients.

What interested you in the drug? Because you’re always looking for new drugs.

This drug’s treatment duration is very, very long, only one drug, that is a great advantage. Also the current study, we evaluated the impact of duration of drug iinterruption on the efficacy of lenvatinib in patients who enrolled in the SELECT trial. That is a randomised clinical trial comparing lenvatinib over placebo in patients with radioactive iodine refractory DTC.

How many patients were in the study?

About 392 patients were randomly assigned in a two to one ratio to lenvatinib or placebo.

That’s a big number of patients.

A big number, yes.

You’re a busy clinic! Then the data was opened and looked at when?

Yes, the primary result was already published in The New England Journal of Medicine and there are a lot of subgroup analyses also published.

The evidence is clear for the survival benefit, what about the side effects and what does the patient feel and is it tough going?

The most common grade 3 adverse events included hypertension, decreased appetite and decreased weight and proteinuria. But most toxicity was manageable by dose modification or drug interruption so I do think this drug is manageable.

And patients complied and they continued to go on? What happens when you interrupt the drug? You delay it by a while or you change the dose?

Some patients needed dose reduction but some patients needed to keep the dose because during the dose reduction some patients developed disease progression. So dose intensity is very important to keep the treatment.

And you did some subset analyses, is it too early to talk about that?

Multivariant analysis indicated that the duration of drug interruption is a significant factor in the efficacy of lenvatinib.

So you have to be careful about that.

Yes. Also the Kaplan-Meier curve according to duration of drug interruption demonstrated progression free survival is better in patients who had less than fourteen days of drug interruption than that of patients who had longer drug interruption.

So what’s your advice to other head and neck specialists all over the world who will be watching this video?

The results from our study indicated that a long period of drug interruption may negatively impact the potential benefit of lenvatinib. So we have to reduce the duration of drug interruption. Also when adverse events become severe patients’ quality of life worsened leading to drug interruption or treatment discontinuation. So to reduce the severity of adverse events both early recognition of adverse events and appropriate management of toxicity are essential.

And you think now that this is the drug of choice for the treatment of radio iodine resistant thyroid cancer.

That’s right.