The progression-free survival (PFS) benefit with lenvatinib over placebo in patients with radioactive iodine (RAI)–refractory differentiated thyroid cancer (DTC) was sustained in an updated analysis of the phase III SELECT trial presented at the 2016 ASCO Annual Meeting.
The updated outcomes showed a 15.7-month median PFS benefit with the multikinase inhibitor versus placebo. The overall response rate (ORR) was 60.2% with lenvatinib, and the median duration of response (DOR) was 30 months.
“Based on the data shown here, patients who respond to lenvatinib can have very prolonged, durable responses. This may be one consideration for physicians as they assess the most appropriate treatment for their patients,” the authors wrote in the conclusion on their ASCO poster.
The SELECT trial randomized 392 patients with advanced RAI-refractory DTC in a 2:1 ratio to oral lenvatinib at 24-mg daily in 28-day cycles (n = 261) or placebo (n = 131). Pretreatment with 1 prior TKI regimen was allowed. Baseline characteristics were similar between the 2 arms.
For the primary analysis, the data cutoff was November 15, 2013, after which patients receiving lenvatinib could continue treatment and patients in the placebo arm could cross over to receive lenvatinib at progression. The cutoff date for the updated analysis presented at ASCO was August 31, 2015. At the data cutoff, there were 261 patients in the lenvatinib group and 131 patients in the placebo arm.
In the updated results, the median PFS was 19.4 months (95% CI, 14.8-29.3) with lenvatinib versus 3.7 months (95% CI, 3.5-5.4) with placebo (HR, 0.24; 99% CI, 0.17-0.35; P
<.0001). Among patients treated with lenvatinib who had either a complete response (CR) or a partial response (PR), the median PFS was 33.1 months (95% CI, 27.8–not estimable). The median PFS was 7.9 months (95% CI, 5.8-10.7) among patients in the lenvatinib arm who did not have a PR or CR.
There were 157 patients (60.2%; 95% CI, 54.2-66.1), who responded in the lenvatinib arm, including 5 CRs (1.9%) and 152 PRs (58.2%). The stable disease (SD) rate was 30.3% (n = 79) and the durable SD rate was 21.8% (n = 57). Ten patients (3.8%) had progressive disease.
The ORR in the placebo arm was 2.3% (n = 3; 95% CI, 0-4.9), including 1 CR (0.8%) and 2 PRs (1.5%). The SD rate was 58.8% (n = 77) and the durable SD rate was 38.9% (n = 51). Forty-five patients (34.4%) had progressive disease.
The disease control rate was 90.4% (n = 236) in the lenvatinib cohort and 61.1% (n = 80) in the placebo group. The clinical benefit rates were 82% (n = 214) and 41.2% (n = 54), respectively.
The median DOR was 30 months (95% CI, 18.4-35.2) among patients treated with lenvatinib. The DOR was generally consistent across patient subgroups defined by age, sex, baseline tumor subtype (papillary or follicular), and baseline ECOG performance status.
However, DOR was shorter in patients with greater disease burden and those with liver metastases. Among patients with a tumor size of ≤35 mm, 35 mm to 60 mm, 60 mm to 92 mm, and >92 mm, the DOR was not estimable, 27.5 months, 18 months, and 15.7 months, respectively. The DOR was 15.7 months in patients with liver metastases compared with 31.3 months in patients without liver metastases.
In their ASCO poster, the researchers also reported outcomes for 2 patients with a prolonged response to lenvatinib.
The first patient was a 57-year-old white man with stage III Hürthle cell follicular thyroid cancer who had received no prior VEGF therapy. The patient had multiple metastases in the lung, abdomen, and bone. He had received lenvatinib since July 2012 and had achieved a PR with a PFS of 44+ months. As of May 2016, he was still receiving lenvatinib and his last instance of disease progression occurred prior to the start of the study.
The second patient was a 59-year-old white woman with stage III Hürthle cell follicular thyroid cancer with neck and lung metastases. She had no prior VEGF therapy. She has received lenvatinib since November 2011. The patient achieved a CR with a PFS of 51+ months. As with the first patient, she has also still been receiving lenvatinib as of May 2016 and her last instance of disease progression was also before the start of the study.
“Together with the efficacy analyses presented here, these case studies demonstrate that the response to lenvatinib treatment in patients with RAI–refractory DTC can be both quick and prolonged,” the researchers wrote.
Based on the primary analysis of the SELECT trial, the FDA approved lenvatinib as a treatment for patients with progressive, RAI-refractory DTC in February 2015.
In the primary analysis, lenvatinib reduced the risk of disease progression by 79% (HR = 0.21; 99% CI, 0.14-0.31; P <.0001). At a median treatment duration of 13.8 months with lenvatinib and 3.9 months with placebo, the median PFS was 18.3 months versus 3.6 months, respectively.
The safety profile for the primary analysis showed that 97.3% of patients receiving lenvatinib and 59.5% of patients on placebo experienced a treatment-related adverse event (AE), with grade ≥3 AE rates of 75.9% and 9.9%, respectively.
The most frequently reported grade ≥3 AEs in the lenvatinib group included hypertension (42.9% vs 2.3%), proteinuria (10.0% vs 0), decreased weight (9.6% vs 0), fatigue (9.2% vs 2.3%), and diarrhea (8.0% vs 0).
There were 6 patient deaths in the lenvatinib arm considered to be treatment related. These included 1 pulmonary embolism, 1 hemorrhagic stroke, 1 related to a general deterioration of health, and 3 in which no specific cause was identified.
Gianoukakis AG, Mathias EG, Dutcus, et al. Response to lenvatinib treatment in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC): updated results from SELECT. J Clin Oncol 34, 2016 (suppl; abstr 6089).