Background: Lenvatinib significantly prolonged progression-free survival (PFS) vs placebo in the primary analysis of the phase 3 SELECT study of RR-DTC. Median duration of overall response (DOR; per RECIST 1.1) to lenvatinib was not reached as of the primary analysis. We present new efficacy data with a focus on DOR.
Methods: Data cutoff was 31 August 2015 (lenvatinib: n=261, placebo: n=131); primary endpoint was PFS. DOR was examined for patients with partial (PR) or complete responses (CR) and by subgroup (age, sex, tumor subtype, baseline disease burden, baseline ECOG score, metastasis site, prior VEGF therapy). Tumor assessments were per investigator. Clinical features of 2 patients with prolonged responses to lenvatinib are reported.
Results: Median PFS was 19.4 months (95% CI 14.8–29.3) for lenvatinib and 3.7 months (95% CI 3.5–5.4) for placebo (HR 0.24; 99% CI 0.17–0.35; P<0.0001). 157 Patients (60.2%) responded to lenvatinib (median DOR 30 months; 95% CI 18.4–35.2). 3 Patients (2.3%) responded to placebo (median DOR 14.7 months; 95% CI 7.5–not evaluable [NE; median not yet reached]). Median DOR (months) to lenvatinib was similar among subgroups except in patients with greater disease burden (tumor size ≤35mm: NE; 35–60mm: 27.5; 60–92mm: 18.0; >92mm: 15.7) and liver metastasis (yes: 15.7; no: 31.3). 2 Patients with prolonged DOR are still receiving lenvatinib: 1 woman treated since November 2011 achieved CR (DOR 46 months, ongoing; PFS 48 months); 1 man treated since July 2012 achieved PR (DOR 35 months, ongoing; PFS 41 months). Notably, the patient with PR has metastases in the lung, abdomen, and bone.
Conclusions: In this analysis, lenvatinib PFS benefit was maintained with a notable DOR. The case studies profiled demonstrate that an extended DOR to lenvatinib can occur in patients with RR-DTC who show significant variation in the severity of disease.