Everolimus Survival Benefit Suggested in Updated NET Trial Results

Excerpt:

“Patients with nonfunctioning neuroendocrine tumors (NETs) of lung or gastrointestinal (GI) origin continued to live longer when treated with the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) than with placebo, ongoing follow-up in a randomized trial has shown.

“A second planned interim analysis of the RADIANT-4 trial showed a 27% reduction in the estimated risk of death for patients who received everolimus compared with placebo. However, the difference did not meet the statistical threshold for overall survival (OS) significance.

“As previously reported, the trial met the primary endpoint of progression-free survival (PFS), and a first interim survival analysis showed a trend in favor of the everolimus arm. Follow-up for survival will continue, James C. Yao, MD, a professor at The University of Texas MD Anderson Cancer Center, reported at the 2016 ASCO Annual Meeting.”

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Everolimus–Exemestane Combination Failed to Significantly Extend OS in Advanced Breast Cancer

The gist: A clinical trial with volunteer patients tested a treatment for postmenopausal women with HR-positive, HER-2–negative advanced breast cancer. The treatment combines the drugs everolimus and exemestane. The clinical trial compared it to exemestane alone. The combination did NOT appear to give longer overall survival rates than exemestane alone.

“The addition of everolimus to exemestane extended OS in postmenopausal women with HR-positive, HER-2–negative advanced breast cancer, but the difference was not statistically significant, according to results of the BOLERO-2 study.

“BOLERO-2 is a randomized phase 3, double blind, international trial.

“Prior results showed the addition of 10 mg daily everolimus (Afinitor, Novartis) — an inhibitor of mammalian target of rapamycin (mTOR) — to 25 mg daily exemestane significantly extended PFS compared with exemestane alone (7.8 months vs. 3.2 months; P<.001).

“In the current study, Martine Piccart, MD, PhD, professor of oncology at the Université Libre de Bruxelles in Belgium and director of medicine at Institut Jules Bordet, and colleagues presented OS outcomes as part of a prospectively planned secondary-endpoint analysis.

“Results showed patients assigned the combination demonstrated longer median OS (31 months vs. 26.6 months; HR=0.89; 95% CI, 0.73-1.1), but the difference was not statistically significant.

“ ‘Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting,’ Piccart and colleagues wrote.”


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.


A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1

“The mTOR complex 1 (mTORC1) pathway promotes cell growth in response to many cues, including amino acids, which act through the Rag guanosine triphosphatases (GTPases) to promote mTORC1 translocation to the lysosomal surface, its site of activation. Although progress has been made in identifying positive regulators of the Rags, it is unknown if negative factors also exist. Here, we identify GATOR as a complex that interacts with the Rags and is composed of two subcomplexes we call GATOR1 and -2.”


A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1

“The mTOR complex 1 (mTORC1) pathway promotes cell growth in response to many cues, including amino acids, which act through the Rag guanosine triphosphatases (GTPases) to promote mTORC1 translocation to the lysosomal surface, its site of activation. Although progress has been made in identifying positive regulators of the Rags, it is unknown if negative factors also exist. Here, we identify GATOR as a complex that interacts with the Rags and is composed of two subcomplexes we call GATOR1 and -2.”


A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1

“The mTOR complex 1 (mTORC1) pathway promotes cell growth in response to many cues, including amino acids, which act through the Rag guanosine triphosphatases (GTPases) to promote mTORC1 translocation to the lysosomal surface, its site of activation. Although progress has been made in identifying positive regulators of the Rags, it is unknown if negative factors also exist. Here, we identify GATOR as a complex that interacts with the Rags and is composed of two subcomplexes we call GATOR1 and -2.”