In February 2016, the FDA approved
Afinitor (everolimus) tablets for the treatment of adult patients with progressive, well-differentiated, nonfunctional neuroendocrine tumors (NETs) of gastrointestinal or lung origin that are unresectable, locally advanced or metastatic.
Neuroendocrine tumors arise from cells in the endocrine or nervous system, and most commonly occur in the intestine. They can also, however, derive from the lung, pancreas, and other parts of the body.
The approval of Afinitor was largely based on results from the phase 3 RADIANT-4 study showing the drug to improve median progressive free survival (PFS) when compared to placebo (11.0 months vs 3.9 months, respectively). Those results were published in the March 2016 edition of the Lancet
This week in the Lancet
, new quality of life data from the RADIANT-4 was published, indicating that the drug does not improve patients’ quality of life as much as its impressive efficacy data would infer.
RADIANT-4 was a randomized, double-blind, placebo-controlled, phase 3 trial involving 302 patients at 97 centers in 25 countries. Adults (aged ≥18 years) were eligible for the study if they had pathologically confirmed, advanced, non-functional, grade 1 or 2 NETs of lung or gastrointestinal origin. Patients received oral everolimus (10 mg per day) or placebo. Health-related quality of life (HRQOL) scores were assessed with the Functional Assessment of Cancer Therapy—General (FACT-G).
The prespecified secondary outcome measure for the study was the time to definitive deterioration (≥7 points) in FACT-G total score and the study observed in the Afinitor-treated group that time was 11.27 months compared to 9.23 months in the control group (P
The findings indicate that while the approved drug does delay disease progression by a significant margin that is balanced with a non-significant improvement in quality of life.
Common adverse events associated with Afinitor in NETs patients are stomatitis, infections, diarrhea, peripheral edema, fatigue, rash, cough, nausea, asthenia, pyrexia, decreased appetite, decreased, weight, and dyspnea.
Afinitor is also approved for treating:
- postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole.
- adults with progressive neuroendocrine tumors of pancreatic origin
- adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib
- adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.
- Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016;387:968-977. DOI: http://dx.doi.org/10.1016/S0140-6736(15)00817-X
- Pavel ME, Singh S, Strosberg JR, et al. Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Published August 21, 2017 ahead of print. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30471-0
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