Does cabozantinib have potential to become a first-line treatment for metastatic renal cell carcinoma?
- Cabozantinib was tested in patients with intermediate and poor-risk metastatic renal cell carcinoma (mRCC)
- Progression-free survival and response rate was significantly improved in patients receiving cabozantinib versus sunitinib
- Results suggest that cabozantinib could be suitable first line for mRCC
At the 2016 Annual Congress of the European Society for Medical Oncology (ESMO) Dr Toni Choueiri, Director of the Kidney Cancer Center, Dana-Farber Cancer Institute, Boston, presented data which could have implications for how mRCC is treated first line. Dr Choueiri summaries the results by stating “cabozantinib did improve progression-free survival and overall response compared to sunitinib.”
Sunitinib, the current standard of care, is a small-molecule inhibitor of tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors. Cabozantinib however, while still inhibiting tyrosine kinases, also inhibits the MET and AXL receptors; both of which are involved in promoting metastasis and angiogenesis.
“…response rate was statistically significant, and higher with cabozantinib; 46% versus 18% with sunitinib.”
Dr Toni Choueiri, Director, Kidney Cancer Center, Dana-Farber Cancer Institute, Boston, US
The CABOzantinib versus SUNitinib (CABOSUN) study was conducted by the Alliance for Clinical Trials in Oncology, part of Exelixis’ collaboration with the National Cancer Institute (NCI) Cancer Therapy Evaluation Program. Dr Choueiri and his team tested the two agents in 157 patients with previously untreated, clear-cell mRCC.
Patients had an ECOG performance status of 0-2 and were at intermediate or poor risk, according to International mRCC Database Consortium Criteria. 36% had bone metastases. In the phase II trial, patients were randomised to receive cabozantinib (60 mg daily) or sunitinib (50 mg daily; 4 weeks on, 2 weeks off).
The primary endpoint was progression-free survival (PFS), as assessed by investigators. Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety.
The study met its primary endpoint; cabozantinib significantly reduced the median rate of progression or death by 31% compared to sunitinib (adjusted hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48-0.98, one-sided P=0.012). PFS was 8.2 months (95% CI 6.2-8.8) in the cabozantinib arm and 5.6 months (95% CI 3.4-8.2) in the sunitinib arm.
“In addition,” Dr Choueiri says, “response rate was statistically significant, and higher with cabozantinib; 46% versus 18% with sunitinib,” (46%; 95% CI 34-57% vs 18%; 95% CI 10-28%).
OS results are only preliminary, but Dr Choueiri believes that the trend suggests that results will be in favour of cabozantinib (median OS 26.4 months for cabozantinib vs 23.5 months for sunitinib; HR 0.87, 95% CI 0.55-1.4).
Adverse events appeared to be similar in both lines of treatment. Grade 3 or 4 adverse events occurred in 65% of patients receiving cabozantinib versus 68% with sunitinib. Those most frequently reported across both treatment arms were hypertension, diarrhoea and fatigue. A total of 16 patients from both groups discontinued treatment.
The study will undoubtedly raise questions; such as can this analysis also apply to patients in the good-risk group for mRCC? The results presented could mean that cabozantinib, currently approved for the treatment of mRCC second line in the EU and US, could be considered for first-line treatment in the future.
Dr Choueiri finished by acknowledging the support that the study received. “I really want to give kudos to the Alliance and to the NCI for pushing us and thinking deeply about the problem and the unmet need, and sponsoring [us] to do such studies.”
Based on Choueiri T, Halabi S et al. CABOzantinib versus SUNitinib (CABOSUN) as initial targeted therapy for patients with metastatic renal cell carcinoma (mRCC) of poor and intermediate risk groups: Results from ALLIANCE A031203 trial (LBA30_PR).
Presented on Monday 10 October 2016.
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