Drug Everolimus Does Not Improve Overall Survival in Patients with Advanced Liver Cancer

“Despite strong preclinical data, the drug everolimus failed to improve overall survival in patients with advanced liver cancer, compared to placebo, according to a study in the July 2 issue of JAMA.

“Patients with advanced hepatocellular carcinoma (HCC; a type of liver cancer) have a median overall survival of less than l year, largely because of the absence of effective therapies. The drug sorafenib is the only systemic therapy shown to significantly improve overall survival in advanced HCC; however its benefits are mostly transient and modest, and disease eventually progresses. In preclinical models, everolimus prevented tumor progression and improved survival, according to background information in the article.

“Andrew X. Zhu, M.D., Ph.D., of the Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, and colleagues randomly assigned 546 adults with advanced HCC whose disease progressed during or after sorafenib or who were intolerant of sorafenib to receive everolimus (n = 362) or placebo (n = 184), both given in combination with best supportive care and continued until disease progression or intolerable toxicity. In this phase 3 study, patients were enrolled from 17 countries between May 2010 and March 2012.

“The researchers found no significant difference in overall survival between the two groups…”

Editor’s note: This article describes a clinical trial with volunteer patients to test a potential new liver cancer drug called everolimus. Patients in the trial all had advanced hepatocellular carcinoma (HCC) and had been unsuccessfully treated with sorafenib. Half were given everolimus, and for comparison, half were given a “fake” placebo drug. Unfortunately, there was no significant difference in survival between the two groups.


Lung Cancer Drug Retaspimycin Fails Clinical Trial

A phase II clinical trial found no survival benefit for the lung cancer drug retaspimycin in non-small cell lung cancer (NSCLC). The trial examined NSCLC patients with a history of smoking who were given the chemotherapy agent docetaxel (Taxotere) either with or without retaspimycin. Adding retaspimycin did not improve overall survival in NSCLC patients in general or in the subset of patients with squamous cell carcinoma (a type of NSCLC closely linked to smoking). The company will complete enrollment in a separate study investigating retaspimycin in combination with everolimus (Afinitor) by the end of 2013, but will begin no further clinical trials with retaspimycin.


'Super Responders' May Hold Clues for Cancer Treatment

In rare, previously unexplained cases, individual cancer patients respond to treatment much better than others do. Now, faster and cheaper DNA sequencing is allowing researchers to search the entire genetic material of such patients for the causes of their ‘super responder’ status. In one case, researchers linked one patient’s exceptional response to Afinitor (everolimus) to a mutation in the TSC1 gene. They plan to develop a test for this mutation, hoping to identify other cancer patients who will respond strongly to Afinitor. Such studies may resurrect drug candidates that were abandoned after clinical trials, where they were ineffective in most, but very effective in a few patients. Clinical trials and clinics focusing specifically on super responders are being planned.


mTOR Inhibitors May Be Associated with Kidney Injury

A class of cancer drugs called mTOR inhibitors may produce kidney toxicity in at least some patients. mTOR inhibitors, including rapamycin (sirolimus/Rapamune), temsirolimus (Torisel), everolimus (Afinitor), and ridaforolimus, are used to treat certain forms of breast and kidney cancer, and are under investigation for several other cancers. Researchers described four cases of patients treated with mTOR inhibitors developing severe acute kidney injury. They recommend that doctors carefully monitor kidney function in patients receiving these drugs. However, other experts emphasize that it is unclear whether the mTOR inhibitors were indeed the cause of the kidney injury. In at least one case, the patient was also taking other drugs known to cause kidney toxicity.


mTOR Inhibitors May Be Associated with Kidney Injury

A class of cancer drugs called mTOR inhibitors may produce kidney toxicity in at least some patients. mTOR inhibitors, including rapamycin (sirolimus/Rapamune), temsirolimus (Torisel), everolimus (Afinitor), and ridaforolimus, are used to treat certain forms of breast and kidney cancer, and are under investigation for several other cancers. Researchers described four cases of patients treated with mTOR inhibitors developing severe acute kidney injury. They recommend that doctors carefully monitor kidney function in patients receiving these drugs. However, other experts emphasize that it is unclear whether the mTOR inhibitors were indeed the cause of the kidney injury. In at least one case, the patient was also taking other drugs known to cause kidney toxicity.


mTOR Inhibitors May Be Associated with Kidney Injury

A class of cancer drugs called mTOR inhibitors may produce kidney toxicity in at least some patients. mTOR inhibitors, including rapamycin (sirolimus/Rapamune), temsirolimus (Torisel), everolimus (Afinitor), and ridaforolimus, are used to treat certain forms of breast and kidney cancer, and are under investigation for several other cancers. Researchers described four cases of patients treated with mTOR inhibitors developing severe acute kidney injury. They recommend that doctors carefully monitor kidney function in patients receiving these drugs. However, other experts emphasize that it is unclear whether the mTOR inhibitors were indeed the cause of the kidney injury. In at least one case, the patient was also taking other drugs known to cause kidney toxicity.


Phase II Study of Docetaxel in Combination with Everolimus for Second- or Third-Line Therapy of Advanced Non–Small-Cell Lung Cancer

We conducted a phase II study of docetaxel in combination with everolimus, a mammalian target of rapamycin (mTOR) inhibitor, for salvage therapy of advanced non–small-cell lung cancer (NSCLC) based on promising preclinical and early-phase clinical data. The combination of everolimus and docetaxel was tolerated well, but the efficacy was relatively modest in an unselected population of patients with NSCLC.


Taxotere-Afinitor Combination Only Modestly Effective in Advanced NSCLC

A phase II clinical trial examined the use of the chemotherapy drug docetaxel (Taxotere) combined with everolimus (Afinitor), a member of a family of drugs called mTOR inhibitors, as second- or third-line treatment in advanced non-small-cell lung cancer (NSCLC). The treatment was well tolerated, but only modestly effective compared to standard therapy in similar patients. The patients in the study had not been selected for any specific biomarkers; better effectiveness may be achieved in patients with relevant biomarkers.