Lenvatinib monotherapy fails to improve survival in anaplastic thyroid cancer
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Adults with anaplastic thyroid cancer who received lenvatinib monotherapy experienced some tumor shrinkage but were not considered responders to treatment, suggesting combination therapy should be investigated, researchers reported.
The findings, from an international cohort of 34 patients, differed from a small, phase 2 study conducted in Japan that demonstrated 24% of participants achieved a partial response with lenvatinib (Lenvima, Eisai) therapy, Lori J. Wirth, MD, the Elizabeth and Michael Ruane endowed chair of medical oncology, medical director of Massachusetts General Hospital’s Center for Head and Neck Cancers, and associate professor of medicine at Harvard Medical School, said during a presentation at ENDO Online.
“We did not see promising, single-agent activity of lenvatinib in anaplastic thyroid carcinoma,” Wirth told Healio. “There may be a role for lenvatinib in this aggressive entity, but if so, we’ll need to identify a more effective combinatorial approach.”
In an open-label, phase 2 study, Wirth and colleagues analyzed data from 34 adults with a histologic diagnosis of anaplastic thyroid cancer who received 24 mg lenvatinib once daily (median age, 67 years; 21 women; 27 white). Most participants had received treatment with one or two prior cancer regimens (n = 20). The primary endpoint was confirmed objective response rate (ORR), determined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Researchers conducted an interim analysis after the first 20 participants completed at least two tumor assessments at baseline and 6 weeks, or discontinued treatment.
Researchers stopped the study for futility when the minimum threshold for ORR (15%) was not met at the interim analysis; one participant experienced unconfirmed partial response, for an ORR of 5% (95% CI, 0.1-24.9), Wirth said. Within the full cohort, one participant had a confirmed partial response, for an ORR of 3% (95% CI, 0.1-15.8).
Wirth said median progression-free survival for the interim analysis cohort and the total cohort was 2.6 months for both; median overall survival was 2.9 and 3.2 months, respectively. Seven participants experienced 22% to 63% shrinkage in tumor measurements, but did not meet response criteria.
“There were a couple of patients who experienced tumor shrinkage on lenvatinib, but this activity was not durable,” Wirth said. “This suggests that lenvatinib can potentially be augmented if given in combination with another agent, and because we’re seeing lenvatinib/pembrolizumab [Keytruda, Merck] activity in multiple other solid tumors, and anti-PD-1 activity in anaplastic thyroid carcinoma, lenvatinib/pembrolizumab is of future interest.”
All participants experienced at least one treatment-emergent adverse event, with 94% of participants experiencing treatment-related adverse events. Treatment-related adverse events led to dose reduction for 14 participants (41%) and dose interruption for 19 participants (56%).
“There were no treatment-related deaths, and no major treatment-related bleeding events occurred,” Wirth said, adding that the observed adverse events were consistent with the safety profile of lenvatinib or progression of anaplastic thyroid cancer.
“Due to a lack of efficacy observed with lenvatinib monotherapy in anaplastic thyroid cancer, further investigation of lenvatinib in combination with a checkpoint inhibitor may be warranted, rather than pursuing lenvatinib as a single agent alone,” Wirth said.
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Wirth LJ, et al. An open-label, single-arm, multicenter, phase 2 trial of lenvatinib for the treatment of anaplastic thyroid cancer. ENDO Online; June 8-19, 2020.
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