Everolimus plus Endocrine Therapy: Effective 1st Line Option for Postmenopausal Women with HR+/HER2- Advanced Breast Cancer

MedicalResearch.com Interview with:

Melanie E. Royce, MD, PhD Division of Hematology/Oncology University of New Mexico Comprehensive Cancer Center Albuquerque

Dr. Royce

Melanie E. RoyceMDPhD
Division of Hematology/Oncology
University of New Mexico Comprehensive Cancer Center
Albuquerque

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: BOLERO-4 is an open label, single-arm, Phase II study that evaluates the combination of everolimus plus letrozole as a first-line treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor (HER2)-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the BOLERO-4 trial published in JAMA Oncology showed that everolimus in combination with endocrine therapy is an effective first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer.

A total of 202 patients received everolimus in combination with letrozole as first-line treatment between March 7, 2013 and December 17, 2014. Median progression-free survival (PFS) in the first-line setting was 22.0 months (95% CI 18.1-25.1) with an overall response rate of 45% (95% CI 38.1-52.2) and clinical benefit rate of 74% (95% CI 67.7-80.1). A total of 152 (75%) discontinued treatment, primarily due to disease progression (51%) or adverse events (16%).

Data from a smaller number of patients in BOLERO-4 also show limited efficacy with continued everolimus, combined with exemestane, following disease progression.
Second-line treatment was ongoing in 16 (32%) patients, while 34 (68%) had discontinued. The most frequent reason for second-line treatment discontinuation was disease progression (56%). In the second-line setting, median PFS was 3.7 months (95% CI 1.9-7.4) with an overall response of 6% (95% CI 1.3-16.5) and clinical benefit rate of 28% (95% CI 16.2-42.5).

Safety findings from BOLERO-4 are consistent with previous studies of Afinitor in advanced breast cancer. The most common (≥ 20% incidence) first-line all-grade adverse events were stomatitis (69%), weight loss (44%), nausea (37%) and anemia (35%). Most were ‘low grade’ in severity (grade 1 or 2) and generally well managed. Safety findings show the most common (≥ 10% incidence) second-line adverse events were stomatitis (20%) and weight loss (20%). Lower rates of stomatitis in second-line were noted.  Continue reading

Lutathera® Approved for Neuroendocrine Tumors of the Pancreas (Steve Job’s Cancer)

MedicalResearch.com Interview with:

Dr- Lynn Matrisian

Dr. Matrisian

Lynn Matrisian, PhD, MBA
Chief science Officer
Pancreatic Cancer Action Network

MedicalResearch.com: Would you tell us a little about PNETs? How common is this type of pancreatic tumor? How does Lutathera differ from other treatments for this tumor? 

Response: Pancreatic neuroendocrine tumors (PNETs) make up about 6 percent of all pancreatic cancer diagnoses. They are less common and slower growing than the more common type of pancreatic cancer, adenocarcinoma, and have a better prognosis.

Lutathera® is a peptide receptor radionuclide therapy (PRRT) that was approved for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including PNETs, that express somatostatin receptors. The drug is a somatostatin analog that is conjugated to a radionuclide (177Lu) to selectively deliver radiotherapy to the cancer cells.

Other treatment options for PNETs include surgery (partial or complete removal of the tumor), chemotherapy (typically in combination) or radiation therapy (conventional as well as PRRT). Patients may also receive targeted therapies. Sutent® blocks platelet-derived growth factor receptors (PDGFRs) α and β, stem-cell factor receptor (c-kit) and vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3, leading to inhibition of cell growth and angiogenesis. Afinitor® behaves as a rapamycin analog, blocking the mammalian target of rapamycin (mTOR) signaling pathway.

Prior to Lutathera’s approval, there were two non-PRRT somatostatin analogs approved for PNET patients. These drugs were initially intended to mitigate some of the symptoms of the disease, but they were also found to slow the cancer cells’ growth. The approved somatostatin analogs are lanreotide and octreotide.  Continue reading