ECC 2015: Cabozantinib Improves Survival in Patients With Advanced Kidney Cancer


Key Points

  • The estimated median progression-free survival time was 7.4 months for patients with advanced clear cell kidney cancer who received cabozantinib, compared with 3.8 months for those receiving everolimus.
  • The objective response rate was 21% for cabozantinib and 5% for everolimus.
  • An interim analysis of overall survival among all of the 658 patients found that it was one-third better for patients receiving cabozantinib.

Patients with advanced kidney cancer lived for nearly twice as long without their disease progressing if they were treated with cabozantinib (Cometriq), a drug that inhibits the action of tyrosine kinases. Toni Choueiri, MD, presented the research (Abstract 4LBA) at the Presidential Session of the 2015 European Cancer Congress in Vienna, Austria.

The research described results from the first 375 patients of a total of 658 patients recruited to the phase III clinical METEOR trial comparing cabozantinib with everolimus (Afinitor), the current standard treatment for the disease.

Analysis of results in July 2015 showed that the estimated median progression-free survival time for patients with advanced clear cell kidney cancer, randomly assigned to receive cabozantinib, was 7.4 months, compared with 3.8 months for those receiving everolimus. The objective response rate was 21% for cabozantinib and 5% for everolimus. An interim analysis of overall survival among all of the 658 patients found that it was one-third better for patients receiving cabozantinib. The findings were published simultaneously with the 2015 European Cancer Congress presentation by Choueiri et al in The New England Journal of Medicine.

Dr. Choueiri, Associate Professor of Medicine at Harvard Medical School and Clinical Director and Kidney Cancer Center Director at The Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, said, “I am very excited about the outcome of the study since the results may change the standard of care in patients with advanced kidney cancer who have received prior standard therapy that targets the vascular endothelial growth factor receptor (VEGFR).”

Cabozantinib and the METEOR Trial

“Although treatment with VEGFR-targeted drugs has been very effective in the first line of therapy for patients with advanced kidney cancer, in many cases tumour cells find ways to escape control by these drugs. Cabozantinib is a new drug that targets possible escape mechanisms of tumour cells, including the tyrosine kinases MET, VEGFR, and AXL. The results of the METEOR trial indicate that cabozantinib is able to shrink tumors and slow down tumor growth much better than current standard treatment in patients who previously received VEGFR-targeted drugs. This has resulted in a significant reduction in the rate of disease progression or death in the cabozantinib arm as compared with the everolimus arm. Regaining tumor control after prior targeted therapy may reduce symptoms related to kidney cancer and eventually help patients live longer.”

“An early evaluation of overall survival from the ongoing METEOR trial has shown a strong trend indicating that survival may be improved in patients receiving cabozantinib compared to standard therapy. The final evaluation regarding survival will occur at a later time when the data have further matured with longer follow up of the patient population. Overall, these results should give new hope to patients diagnosed with advanced kidney cancer as cabozantinib may become a new treatment option.”

Patients recruited to the METEOR clinical trial, which started in June 2013, were randomized to receive either 60 mg daily of cabozantinib, in tablet form, or 10 mg daily of everolimus, also in tablet form. Their disease had to have progressed within 6 months of receiving prior treatment with VEGFR tyrosine kinase inhibitor therapy.

The METEOR trial is also evaluating the safety of the treatment. The incidence of serious side effects was similar for both drugs, and discontinuation of treatment due to side effects occurred in 9.1% of cabozantinib and 10% of everolimus patients. The most common serious side effects for patients receiving cabozantinib were abdominal pain (3%), abnormal amounts of fluid around the lungs (2.7%), and diarrhea (2.1%); for patients receiving everolimus, they were anemia (3.7%), shortness of breath (3.7%), and pneumonia (3.7%).

Dr. Choueiri said, “The METEOR results are important from a clinical and scientific point of view. Overcoming mechanisms of tumor escape or resistance to standard therapies is critical for improving long-term outcome for our patients with advanced kidney cancer. Further studies include a randomized phase II study of cabozantinib vs standard of care with sunitinib as a first treatment for advanced renal cell cancer. Combinations with other emerging therapies, such as agents boosting the immune system, are of interest, and an early stage clinical trial combining cabozantinib with immune checkpoint inhibitors has been initiated in urological cancers, including patients with kidney cancer.”

The trial has stopped recruiting patients, and researchers are hoping that cabozantinib may become available to patients with advanced kidney cancer some time in 2016. The U.S. Food and Drug Administration has designated it as a Breakthrough Therapy, which may allow expedited development of the drug.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.