Lenvatinib demonstrated a longer median overall survival compared with palliative therapy in patients with stage IVC anaplastic thyroid cancer, a rare disease for which the survival rate has not improved in roughly 20 years. The introduction of targeted therapy to the treatment landscape for anaplastic thyroid cancer has been challenging in the past because some patients do not have time to undergo therapy on a clinical trial because the process is time-consuming, and the procedure for study enrollment may exceed time to progression.
Lenvatinib (Lenvima) demonstrated a longer median overall survival (OS) compared with palliative therapy in patients with stage IVC anaplastic thyroid cancer (ATC), a rare disease for which the survival rate has not improved in roughly 20 years. The introduction of targeted therapy to the treatment landscape for ATC has been challenging in the past because some patients do not have time to undergo therapy on a clinical trial because the process is time-consuming, and the procedure for study enrollment may exceed time to progression.
The OS improvement was demonstrated in a Japanese study of lenvatinib in ATC. The study included 32 patients who were divided into the lenvatinib group (n = 16), and the palliative-care group (n = 16). In patients who received lenvatinib, the median OS was 4.2 months compared with 2.0 months in the palliative-care group (P= .00298), a survival benefit that the study investigators found to be statistically significant. Lenvatinib also resulted in a reduction in tumor size of ≥30% in 31.3% of the patients (n = 5), which was considered to be a clinical partial response. In the palliative care group, no clinical partial responses were observed.
The median OS patients varied among those patients who had a calcification pattern and those who did not. Those with eggshell calcification (n = 11) or lumpy calcification (n = 8) had a 5.5-month median OS when treated with lenvatinib. Those receiving lenvatinib with no calcification had a median OS of only 3 months (P= .0473).
Lenvatinib was administered for a median of 107 days (range 30-837 days). Among the patients who received lenvatinib, 7 had fistula formation (43.8%), 2 experienced bleeding (12.5%), and 1 developed mediastinitis (6.3%). Three patients in the lenvatinib group died due to treatment-related adverse events (AEs), according to the toxicity analysis. There were 13 additional deaths, which the investigators determined to bedisease specific. Patients also experienced other complications, such as brain metastases, which occurred in 2 patients, 2 cases of aspiration pneumonia, and 1 development of suffocation. One patient discontinued treatment on lenvatinib after developing grade 4 digestive tract bleeding. Doses of lenvatinib were either reduced or discontinued for other grade ≥3 AEs.
Seven patients in the palliative care group received a dose of paclitaxel at 80 mg/m2 weekly. However, therapy was only administered 1 to 7 times. The entire cohort had progressive disease, which led to discontinuation of treatment.
Examining the treatment landscape for ATC, the investigators wrote, “In addition to than lenvatinib, BRAF inhibitors serve as effective therapeutic agents for type I ATC withBRAFmutations. Programmed death‑1 (PD-1) checkpoint blockers may also be efficacious in patients with aggressive forms of thyroid cancer. However, these agents are not approved for use in Japan. The combination of PLX4720 and dasatinib induced apoptosis, increased immune cell infiltration, and reduced tumor volume in a preclinical model of ATC, and may be expected to be approved as treatment for patients with ATC in the future.”
Overall, the investigators believe that this study shows progress in the ATC treatment landscape and may rationalize the use of lenvatinib in combination with other agents.
Iwasaki H, Toda S, Suganuma N, et al. Lenvatinib vs. palliative therapy for stage IVC anaplastic thyroid cancer. Mol Clin Oncol. 2020. 12(2):138-143. doi: 10.3892/mco.2019.1964.