Final Cabozantinib OS Results Fail to Show Improvement

June 4, 2015

Cabozantinib failed to significantly increase overall survival compared with placebo in patients with medullary thyroid carcinoma, according to the EXAM study.

Cabozantinib failed to significantly increase overall survival compared with placebo in patients with medullary thyroid carcinoma, according to the final survival analysis of the EXAM study (abstract 6012). However, the drug did significantly improve survival among patients with RET M918T mutations.

Results of EXAM were presented by Martin Schlumberger, MD, of Institut Gustave Roussy in Villejuif, France, and colleagues as a poster presentation at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.

EXAM included 330 patients with unresectable locally advanced or metastatic medullary thyroid carcinoma who were randomly assigned 2:1 to cabozantinib (n = 219) or placebo (n = 111) until disease progression.

The primary endpoint of the study was progression-free survival, which served as the basis of the drug’s approval by the US Food and Drug Administration (FDA). Patients assigned cabozantinib had a median progression-free survival of 11.2 months compared with 4 months for placebo (P < .0001). Overall survival was a secondary endpoint.

Median overall survival was 26.6 months for patients assigned cabozantinib compared with 21.1 months for patients assigned placebo, a non-significant difference (hazard ratio [HR] = 0.85; 95% confidence interval [CI], 0.64–1.12; P = .2409).

The researchers were able to determine RET mutational status in 65% of patients in the trial; 75% of patients with RET mutations harbored RET M918T. Treatment with cabozantinib did result in a significant 25.4-month increase in median overall survival compared with placebo for this subset of patients (HR = 0.60; 95% CI, 0.38–0.94; P = .026). In addition, the researchers noted that this subgroup demonstrated the longest median progression-free survival and the highest response rate.

As with earlier study results, the most frequent adverse events were diarrhea, weight decrease, palmar-plantar erythrodysesthesia syndrome, decreased appetite, nausea, fatigue, dysgeusia, hair color changes, and hypertension. The most common severe adverse events were pneumonia, pulmonary embolism, hypocalcemia, inflammation, dehydration, dysphagia, hypertension, and lung abscess.