Cabozantinib Improved Survival in Medullary Thyroid Cancer With RET Mutations

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Patients with medullary thyroid cancer and RET mutations had better survival when taking cabozantinib.
Patients with medullary thyroid cancer and RET mutations had better survival when taking cabozantinib.

Patients with medullary thyroid cancer who had RET mutations had significantly improved survival when taking cabozantinib, as compared with those without RET mutations, according to new data.

“The results of this study demonstrate for the first time that patients whose tumors are genomically defined to carry the common RET M918T mutation have markedly prolonged survival, increased by more than 2 years, when treated with cabozantinib,” study investigator Steven I. Sherman, MD, who is the associate vice provost of Clinical Research and chair and Naguib Samaan Distinguished Professor in Endocrinology in the Department of Endocrine Neoplasia and Hormonal Disorders at University of Texas MD Anderson Cancer Center in Houston, said in an email interview with Endocrinology Advisor.  

Dr Sherman said the research, which he presented at the 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association, is the first phase 3 trial of patients with thyroid cancer to demonstrate a survival advantage with treatment with a multitargeted kinase inhibitor.

Previously published results from the EXAM study showed cabozantinib increased the overall survival of these patients (HR=0.28; P<.001). The estimated median overall survival for patients who received cabozantinib was 26.6 months vs 21.1 months for placebo (stratified HR=0.85, 95% CI, 0.64-1.12, P=.241).

In this latest phase of the study, Dr Sherman and colleagues set out to evaluate 330 patients with locally advanced or metastatic medullary thyroid cancer. These patients were randomly assigned 2:1 to receive cabozantinib 140 mg daily or placebo.

The median duration of treatment was 10.8 months for patients who received cabozantinib and 3.5 months for patients who received placebo.

The researchers used Sanger and next-generation sequencing to identify RET and RAS mutations, and overall survival was calculated using the Kaplan-Meier method.

RET mutation status was established in 65% of patients, with 79% of those patients having the mutation and 21% not having a RET mutation. Specifically, the most common RET mutation was M918T and was found in 75% of the mutation group.

The overall survival for patients with RET mutations was 31.6 months for patients who received cabozantinib vs 24.8 months for patients who received placebo (HR=0.79, 95% CI, 0.54-1.17; P=.240), according to the study results.

Patients with the RET M918T mutation who received cabozantinib had an improved overall survival of 25.4 months, as compared with the placebo group (HR= 0.60, 95% CI 0.38-0.94; P=.026).

Dr Sherman and colleagues noted an increase in progression-free survival and objective response rate for patients with no RET mutation, but no increase in overall survival.

The researchers identified 16 patients with RAS mutations and observed an increased trend of overall survival in this small subgroup (HR= 0.37; 95% CI, 0.10-1.42; P=.131).

Regarding adverse events in the cabozantinib group, Dr Sherman and colleagues identified 4.2% of patients who developed pneumonia, 3.3% who developed pulmonary embolism, 2.8% who developed hypocalcemia, 2.8% who developed mucosal inflammation, 2.3% who experienced dysphagia, 2.3% who experienced dehydration, 2.3% who developed lung abscess, and 2.3% who developed hypertension.

References

  1. Elisei R, Schlumberger MJ, Müller SP, et al. Cabozantinib in Progressive Medullary Thyroid Cancer. J Clin Oncol. 2013;31(29):3639-3646.
  2. Schlumberger M, Elisei R, Müller S, et al. Final overall survival analysis of EXAM, an international, double-blind, randomized, placebo-controlled phase III trial of cabozantinib (Cabo) in medullary thyroid carcinoma (MTC) patients with documented RECIST progression at baseline. J Clin Oncol. 2015;33(15):Suppl 6012.
  3. Sherman S. Short Oral Communication 51: The Impact Of RET And RAS Mutation Status On Overall Survival In The Exam Trial, A Phase 3 Study Of Cabozantinib (Cabo) In Patients (PTS) With Progressive, Metastatic Medullary Thyroid Cancer (MTC). Presented at: 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association (ITC/ATA); Oct. 18-23, 2015; Lake Buena Vista, Florida.
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