New Options for Advanced Kidney Cancer

Several kidney cancer drugs made the news lately.

The U.S. Food and Drug Administration (FDA) recently approved Inlyta (axitinib) for treating advanced renal cell carcinoma (RCC) after treatment with a systemic therapy has failed. An oral drug made by Pfizer, Inlyta blocks certain receptors that can influence tumor growth and also the progression of kidney cancer. Forty percent to 65 percent of patients whose cancer progresses after first-line therapy go on to receive a second-line treatment, the company said.

In its January announcement, the FDA said that the safety and effectiveness of Inlyta were evaluated in a randomized, open-label, multicenter clinical study of 723 patients whose disease had progressed during or after treatment with an initial systemic therapy. The study was designed to measure the time a patient lived without the cancer progressing. The results showed a median progression-free survival period of 6.7 months, compared with 4.7 months with a standard treatment (sorafenib).

A study presented at the 2012 Genitourinary Cancers Symposium in early February showed that some patients with metastatic RCC may need a higher than standard dose of the newly approved axitinib to achieve optimal benefit, according to an analysis of data from the phase III AXIS trial.

A new combination therapy is also under development. An immunotherapy (AGS-003) agent from Argos Therapeutics combined with the drug sunitinib may help prolong the lives of men with unfavorable-risk, metastatic RCC, according to new data from an open-label, phase 2 study. The study found that the combination of AGS-003 plus sunitinib was linked with a longer survival period than that for sunitinib alone in these patients. The study enrolled 21 patients (16 men) with newly diagnosed metastatic clear-cell RCC.

Multiple partial responses were observed with this combination regimen: 11 of 15 patients (73 percent) who had immune assessments over time showed increases in their CD28+ memory T immune cells, according to Argos. These immune responses correlated directly with longer survival.

Overall, the median progression-free survival was 11.2 months, and the estimated median overall survival was 29.3 months, on the basis of follow-up through January 2012. The combination of immunotherapy and drug is designed to stimulate a patient’s immune response to the tumor. Each production of a patient’s fully personalized immunotherapy generates up to 5 years of treatment for each patient, said Argos.

Lead investigator Robert Figlin, MD, who directs the division of hematology/oncology at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute in Los Angeles, and colleagues found that the combination was tolerated well. Observed adverse events were as expected with sunitinib toxicities, but a notable exception was injection site reactions in approximately 50 percent of study participants.

Preliminary data have been shared about the use of the drug cabozantinib in pretreated patients with metastatic refractory RCC. The patients participated in an ongoing phase 1b trial of cabozantinib, an inhibitor of both MET and VEGFR2 factors. The drug was developed to block metastasis and blood vessel growth in order to kill tumor cells while blocking their escape pathways, Drug Discovery News reported.

The investigators looked at data from patients enrolled in a drug interaction study of cabozantinib in patients with advanced solid tumors. The 25 RCC patients in the trial received 140 mg oral cabozantinib administered daily, and the study endpoints were safety, tolerability, and antitumor activity.

The rate of disease control at week 16 for all 25 patients was 72 percent. An estimate of median progression-free survival was 14.7 months (95 percent confidence interval; lower limit 7.3 months; upper limit was not reached). Ten patients remain in the study and are progression-free, with treatment durations ranging up to 16.4 months, according to Drug Discovery News.

The FDA lists recently approved drugs for the treatment of kidney cancer as sorafenib (2005), sunitinib (2006), temsirolimus (2007), everolimus (2009), bevacizumab (2009), and pazopanib (2009). It looks as though more are on the way.

March 2012 (Vol. 4, Number 3)​