MUNICH — Vandetanib induced tumor shrinkage that persisted throughout multiple treatment lines for patients with advanced unresectable medullary thyroid cancer, according to study results presented at European Society for Medical Oncology Congress.
The agent also appeared safe.
Vandetanib (Caprelsa, Sanofi Genzyme) is a kinase inhibitor approved by the FDA for treatment of patients with symptomatic or progressive medullary thyroid cancer who have unresectable locally advanced or metastatic disease.
Results of the phase 3 ZETA trial demonstrated the agent’s efficacy in advanced medullary thyroid cancer. However, the study had multiple limitations that affect clinical practice, particularly the agent’s use for patients with documented disease progression or beyond first-line therapy for patients who have a worse prognosis.
Jorge Hernando Cubero, MD, oncologist in the department of medical oncology at Vall d’Hebron University Hospital in Barcelona, and colleagues analyzed the efficacy and safety of vandetanib among 59 patients (median age, 48 years; 61% male) with advanced unresectable medullary thyroid cancer include din the Spanish National Database of the Rare Cancer Working Group. All patients had radiologically documented disease progression, and 14% had RET mutations.
Patients initially received vandetanib 300 mg daily, with dose reductions allowed due to toxicity.
Researchers retrospectively reviewed baseline characteristics, PFS, response rate, biomarker correlations and toxicity data for vandetanib treatment in the first-line (61% of patients), second-line (22%) and third-line (17%) settings.
Results showed response rates of 47% in the first-line setting, 53% in the second-line setting and 40% in the third-line setting).
Median PFS was 16.8 months in the first-line setting, 13.6 months in the second-line setting and 11.5 months in the third-line setting.
Researchers observed no correlation between response and calcitonin or carcinoembryonic antigen (CEA). However, a 30% decrease in CEA level from baseline appeared to predict PFS of longer than 11 months (P = .028).
Vandetanib appeared well tolerated, according to researchers.
Twenty-three patients required dose reductions due to toxicity. Most key side effects were grade 1 or grade 2. These included fatigue (22%), skin rash (19%), hypertension (14%) and diarrhea (14%). The most common grade 3 toxicity was oral mucositis (3%).
“Probability of tumor shrinkage with vandetanib is maintained throughout treatment lines, despite a trend of reduced benefit in PFS beyond [the] first line in a cohort of patients with a worse prognosis,” Cubero and colleagues wrote. “CEA reduction may predict longer PFS. Safety is maintained regardless [of] prognosis and prior therapies.” – by Jennifer Southall
Cubero JH, et al. Abstract 1329P. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.
Disclosures: The researchers report no relevant financial disclosures.