AT ECCO2017
AMSTERDAM (FRONTLINE MEDICAL NEWS) – Among patients with advanced renal cell carcinoma (RCC) with metastases to bone, cabozantinib (Cabometyx) was associated with better survival compared with everolimus (Afinitor), according to a subanalysis of data from the METEOR trial .
After 2 years of follow-up, median progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were significantly better for patients with bone metastases who received cabozantinib compared with those who received everolimus, reported Sergio Bracarda, MD, of Presidio Ospedaliero San Donato, Italy, and his colleagues.
“Cabozantinib is a new treatment option for previously-treated patients with advanced RCC with benefits that are maintained in patients with bone metastases,” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.
Previous studies have shown that patients with advanced RCC with bone metastases have generally poor prognosis compared with patients without bone metastases, the authors noted.
As previously reported , the METEOR trial, a randomized phase III study of 658 patients with advanced RCC, showed a significant survival advantage for patients treated with cabozantinib, with a median OS of 21.4 months compared with 16.5 months for patients treated with everolimus, with a hazard ratio (HR) of 0.66 (P = .0003).
In the current sub-analysis, the investigators looked at a subgroup of 142 patients with bone metastases at baseline as seen on CT or MRI. They conducted an exploratory analysis of bone scan response among 162 patients evaluated for bone lesions at baseline by technetium bone scans, and compared the incidence of skeletal-related events (SREs) for 181 patients with a history of SREs, and 477 with no prior SREs. SREs included pathological fractures, spinal cord compression, surgery to bone, and external radiation therapy to bone.
Patients underwent CT or MRI screening every 8 weeks for the first 12 months post randomization, then every 12 weeks thereafter. All patients were screened with technetium bone scans every 18 weeks for the first years, and those patients with bone lesions at baseline were followed with additional scans every 24 weeks.
The authors also looked at serum bone biomarkers, including bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), and C-terminal cross-linked telopeptides of type I collagen.
The median PFS for patients with bone metastases treated with cabozantinib was 7.4 months, compared with 2.7 months for everolimus (HR 0.33, 95% confidence interval [CI] 0.21-0.51). For patients with both bone and visceral metastasis, median PFS was 5.6 months vs. 1.9 months, respectively (HR 0.26, 95% CI, 0.16-0.43).
Median OS for the cabozantinib group was 20.1 months compared with 12.1 months for everolimus (HR 0.54, 95% CI, 0.34-0.84) for patients with bone metastases alone. For patients with both bone and visceral metastases, median OS was 20.1 months with cabozantinib, and 10.7 months with everolimus (HR 0.45, 95% CI, 0.28-0.72).
The ORR with cabozantinib as rated by an independent radiology committee was 17% for patients with bone metastases alone, and 20% for patients with bone and visceral metastases. In contrast, there were no objective responses seen in patients treated with everolimus.
Bone scan responses, defined as a 30% or greater decrease from baseline in bone scan lesion area, were seen in 18% of patients on cabozantinib vs. 10% with everolimus (significance not shown).
Among patients with a history of SREs, 22% had an SRE on cabozantinib, compared with 31% on everolimus. Respective rates among patients without a prior history of SREs were 27% and 15%. At least one SRE occurred in 12% (cabo) and 14% (eve) of patients, including four (cabo) and eight (eve) cases of spinal cord compression. For patients with a history of SREs at randomization, the incidence of postrandomization SREs was 16% (cabo) and 34% (eve) and included zero (cabo) and five (eve) cases of spinal cord compression. Reductions in the bone markers P1NP and CTx were greater with cabo vs. eve. The most common adverse events in patients with bone metastases were consistent with those observed in the overall study population.
The investigators noted that “the safety profile of cabozantinib in the bone metastases subgroup was consistent with the safety profile in the overall population.”
Dr. Bracarda has served as a consultant to Exelixis, which supported the trial and subanalysis. Two coauthors are employees of the company.
