Lenvatinib: 'Real-World' Therapy for Differentiated Thyroid Cancer

Nancy A Meville

September 23, 2016

DENVER — Treatment of radioactive iodine–resistant metastatic differentiated thyroid carcinoma (RMDTC) with lenvatinib (Lenvima, Eisai) in the real-world setting shows consistently encouraging results in progression-free survival; however, side effects, particularly hypertension, early in the course of treatment are common, according to the latest data presented here at the American Thyroid Association 2016 Annual Meeting.

"We have found lenvatinib is an effective therapy in daily clinical practice," said Sina A Jasim, MD, in presenting the findings of results from 25 consecutive patients treated with lenvatinib at the Mayo Clinic, in Rochester, Minnesota, between February 2015 and May 2016.

"Common adverse effects tend to occur early, and dose reductions were frequently required; however, quality of life can be maintained on lenvatinib therapy with proper symptom management and dosage modification," Dr Jasim stressed.

While lenvatinib, a multikinase inhibitor, was approved by the US Food and Drug Administration (FDA) in March 2015 for the treatment of RMDTC based on clinical trials, information is lacking on treatment of the drug in the real-world setting and no postmarketing data have been published regarding efficacy and adverse events in off-study clinical practice.

Another physician presenting a poster at the meeting detailing results in six similar patients treated at his institution told Medscape Medical News that he, too had had to reduce the dose of lenvatinib to control adverse effects, but that the drug nevertheless produced dramatic responses in some patients and that the benefits, so far, seem to outweigh the risks.

Adverse Events: Hypertension Developed in Most Patients

In describing the initial experiences with the drug at the Mayo Clinic, Dr Jasim noted that of the 25 patients, 52% were female, all had previously received radioactive iodine; 14 had papillary cancer, seven were poorly differentiated, three had Hurthle-cell carcinoma, and one follicular.

Among 20 evaluable patients, unconfirmed Response Evaluation Criteria in Solid Tumors Partial Response (RECIST PR) was achieved in 10 patients but confirmed in only six.

Most patients (84%) developed adverse events within the first month of therapy. Consistent with the results of the phase 3 trials for lenvatinib approval, the most common treatment-related adverse effect was hypertension, occurring in 64% (16) of patients.

In 10 patients the hypertension was grade 3 or higher and it was newly onset in seven (14 patients [54%] were on antihypertensives at baseline).

Adjustments to doses of antihypertensive drugs were necessary among six patients (24%) and additions to the doses were required for 12 (48%) in the first 6 weeks of therapy.

"This highlights that frequent contact with patients after lenvatinib initiation during the first 1 to 2 weeks of therapy to monitor and record blood pressure is critical," Dr Jasim said.

Four patients required a therapy interruption of more than 3 weeks, with two cases as the result of cholecystitis, one to diverticulitis, and one to skin lesions.

Eleven patients (41%) required dose reductions due to adverse events, with the median time to the first dose reduction of 33 days (range, 11 to 84). Eight patients (32%) required more than one dose reduction.

The mean duration of therapy with lenvatinib was 6.5 months (range, 1 to 12), with seven patients discontinuing, including one due to disease progression and six due to adverse events: general decline (one); gastrointestinal bleeding (two); diverticulitis (one): fatigue (one); and hemoptysis (one).

Patients' quality of life, measured with the symptom assessment questionnaire (SAQ), which measures quality of life on a scale of 0 to 10 points, with 0 being worst, was administered to patients at each visit.

While the median overall quality-of-life score change at 2 months was not statistically significant (P = .57), fatigue was an exception, with a worsening median score of +2 (range, -2 to +10, P = .007).

"Some Patients Have Had Dramatic Responses"

In his separate poster presentation, Richard J Robbins, MD, professor and chair of the department of medicine and professor at Weill Cornell Medical College and the Methodist Hospital in Houston, Texas, described his center's experience with an initial six patients treated with lenvatinib and reported similar results.

Five of the six patients experienced fatigue, four had hypertension, five had weight loss, two had polycythemia, four had eosinophilia, and five had an increase in thyroid-stimulating hormone (TSH).

In four of the patients the adverse events improved with dose reductions from a starting dose of 24 mg/day to 14 mg/day.

Dr Robbins noted that the improvements with the drug, although preliminary, were impressive, with thyroglobin in one patient dropping from 14,600 ng/mL at baseline to a low of 167 ng/mL, and another patient declining from 3376 to 420 ng/mL.

"Some of the patients have had dramatic responses," he told Medscape Medical News.

"Some have had very rapid and it looks like long-lasting responses, and no one has failed yet, but I'm only out to 17 months with the longest one."

In terms of the side effects, Dr Robbins said reducing the dose was effective.

"For a few patients we had to lower it for a month or two and try to go back. You don't have to stop it altogether — just back off a little bit."

He added that the benefits, so far, seem to outweigh the risks.

"These patients were at a point where they had no other option, and I can say that so far, these are the most dramatic responses I've ever seen."

Dr Jasim and coauthors and Dr Robbins had no relevant financial relationships.

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American Thyroid Association 2016 Annual Meeting; September 22, 2016; Denver, Colorado. Abstract 11, poster 97.

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