Drug combination produces good response rates in advanced papillary renal cell carcinoma (pRCC)
Patients with an advanced form of kidney cancer, for whom there is no standard treatment and a very poor prognosis, respond well to a combination of two existing anticancer drugs, according to new research. This study was presented at 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, in Barcelona, Spain.
The combination of bevacizumab and erlotinib produced excellent response rates with tolerable side effects in patients with advanced papillary renal cell carcinoma (pRCC) and in patients with a highly aggressive form of pRCC called hereditary leiomyomatosis and renal cell cancer (HLRCC). These findings were presented by Ramaprasad Srinivasan, MD, PhD, head of the Molecular Cancer Therapeutics Section, Urologic Oncology Branch, of the National Cancer Institute in Bethesda, Maryland.
"The genetic and biochemical events that lead to papillary renal cell carcinoma are different to those that lead to the more common form of kidney cancer, clear cell renal carcinoma. Treatments that are effective in clear cell RCC are not particularly effective in pRCC,” said Srinivasan. “Some forms of pRCC, particularly those associated with HLRCC, are characterized by altered cellular metabolism; the tumor cells obtain energy from a process called aerobic glycolysis, and they require high levels of glucose to survive. We believe the combination of erlotinib and bevacizumab may target this particular weakness, at least partly, by impairing glucose delivery to the tumor cells."
The researchers recruited 41 patients to a phase II clinical trial of bevacizumab 10 mg/kg, given intravenously once every 2 weeks, combined with erlotinib 150-mg pill taken orally every day. This was continued until disease progression or unacceptable toxic side effects developed. Twenty patients had advanced HLRCC and 21 patients had advanced sporadic (nonhereditary) pRCC. Nineteen of the patients had received at least one previous systemic therapy, such as sunitinib, that had not been successful in preventing disease progression.
"Almost all the patients with HLRCC responded with their tumors either shrinking or remaining stable and not progressing. There was an overall response rate of 65%, with 13 patients showing tumor shrinkage of more than 30% and seven patients with stable disease,” said Srinivasan. “Many of the responses were long-lasting; some of the patients have remained on the study for 3 years or more, which is significant since metastatic HLRCC is uniformly fatal and patients usually die within a year or so.”
Srinivasan stated that approximately a third of the patients with sporadic pRCC had very good partial responses, and many of those were durable. The overall response rate was 29%.
The median length of time that HLRCC patients survived without their disease progressing was 24.2 months, while for the sporadic pRCC patients it was 7.4 months. This compares well with existing survival times for patients on other treatments.
Side effects were mostly mild or moderate and included high blood pressure, acne, proteinuria, and fatigue, which could be managed effectively with drugs or other supportive measures. One patient died from a gastrointestinal hemorrhage, which may have been related to the bevacizumab.