As reported in the Journal of Clinical Oncology by Kreissl et al, a post hoc analysis of outcomes in the pivotal phase III ZETA trial has shown significantly improved progression-free survival with the multikinase inhibitor vandetanib vs placebo in a subgroup of patients with progressive and symptomatic medullary thyroid cancer.
“Vandetanib demonstrated clinical benefit—specifically, increased progression-free survival—in patients with symptomatic and progressive medullary thyroid cancer.”— Kreissl et al
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Study Details
In the ZETA trial, 331 patients with unresectable locally advanced or metastatic medullary thyroid cancer were randomly assigned 2:1 to receive oral vandetanib at a starting dose of 300 mg/d (n = 231) or placebo (n = 100) until disease progression. In the current analysis, patients were divided into four baseline disease severity subgroups: progression and symptoms, symptoms only, progression only, and no progression and no symptoms. The primary outcome measure was progression-free survival among patients with progression and symptoms.
Key Findings
A total of 184 patients had symptomatic and progressive disease at baseline, including 127 in the vandetanib group and 57 in the placebo group. Results with vandetanib for progression-free survival, overall survival, time to worsening of pain, and objective response rate in the subgroup with symptomatic and progressive disease were similar to those observed in the overall study population.
In this subgroup, median progression-free survival was 21.43 months in the vandetanib group vs 8.40 months in the placebo group (hazard ratio [HR] = 0.43, P < .0001). Hazard ratios favored vandetanib in the other three severity subgroups, with a near-significant difference in the symptoms-only subgroup (HR = 0.41, P = .05). Among all patients, median progression-free survival was 22.43 months in the vandetanib group vs 9.68 months in the placebo group.
For overall survival, the hazard ratio for vandetanib vs placebo was 1.08 (P = .71). No significant differences between vandetanib vs placebo were observed in the other three severity subgroups (HRs ranging from 0.77 to 1.12).
For time to worsening of pain, the hazard ratio for vandetanib vs placebo was 0.67 (P = .07). Among other severity subgroups, a significant benefit of vandetanib was observed only in the symptoms-only subgroup (HR = 0.32, P = .02).
Objective response rates were 37% vs 2% (P < .0001) in the symptomatic and progressive subgroup. Among other subgroups, a significant difference was observed only in the progression-only group (48% vs 4%, P = .0001).
The investigators concluded: “Vandetanib demonstrated clinical benefit—specifically, increased progression-free survival—in patients with symptomatic and progressive medullary thyroid cancer.”
Michael C. Kreissl, MD, of University Hospital Magdeburg, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Sanofi Genzyme. For full disclosures of the study authors, visit ascopubs.org.
