“You’ve probably heard about powerful new cancer medicines like Keytruda and Opdivo. As advertisedon TV, these drugs release brakes on the immune system to make tumors disappear and extend survival in deadly diseases like lung cancer and melanoma. But these agents, called checkpoint inhibitors, work in only a fraction of patients. Scientists are searching for diagnostic tests to predict who will be helped, and who won’t.
“A promising solution comes from Foundation Medicine, a molecular diagnostics company headquartered in Cambridge, Mass. Foundation offers a cancer genome profiling test that evaluates mutations in DNA. With results from its standard FoundationOne panel, Foundation calculates a Tumor Mutation Burden (TMB) score. This quantitative readout―based on the number and type of DNA changes per megabase, a length of DNA―may prove helpful to patients considering immune treatment for many advanced forms of cancer.”
“Johns Hopkins Kimmel Cancer Center scientists report data from a new study providing evidence that random, unpredictable DNA copying ‘mistakes’ account for nearly two-thirds of the mutations that cause cancer. Their research is grounded on a novel mathematical model based on DNA sequencing and epidemiologic data from around the world.
” ‘It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer. But it is not as well-known that each time a normal cell divides and copies its DNA to produce two new cells, it makes multiple mistakes,’ says Cristian Tomasetti, Ph.D., assistant professor of biostatistics at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health. ‘These copying mistakes are a potent source of cancer mutations that historically have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.’ ”
“Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) presented data from the ongoing Phase Ib/II clinical trial of sulfatinib in patients with advanced neuroendocrine tumors (“NET”) at the 14th Annual Conference of European Neuroendocrine Tumor Society (“ENETS”), held in Barcelona, Spain from March 8 to 10, 2017. Sulfatinib is an oral, novel angio-immunokinase inhibitor that selectively targets vascular endothelial growth factor receptor (“VEGFR”), fibroblast growth factor receptor (“FGFR”) and colony-stimulating factor-1 receptor (“CSF-1R”), three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion. Five other sulfatinib clinical trials are underway in China and the US, including two Phase III studies in NET patients (SANET-p and SANET-ep), one Phase II study in thyroid cancer patients and one Phase II study in biliary tract cancer patients.”
“The FDA approved telotristat ethyl tablets for use in combination with somatostatin analog therapy for the treatment of adults with carcinoid syndrome diarrhea.
“The approval is intended for patients with carcinoid syndrome — a rare and debilitating condition that affects people with carcinoid tumors and metastatic neuroendocrine tumors — that somatostatin analog therapy alone inadequately controlled. Carcinoid syndrome occurs in less than 10% of patients with carcinoid tumors. The tumors cause the excess release of the hormone serotonin, resulting in diarrhea, which in turn can lead to weight loss, malnutrition, dehydration and electrolyte imbalance.”
“In a phase II study reported at the 2017 Gastrointestinal Cancers Symposium, the tyrosine kinase inhibitor cabozantinib (Cometriq) was evaluated in advanced carcinoid and pancreatic neuroendocrine tumors. Radiographic responses to therapy were observed in both tumor subtypes, and compared to other drugs historically used in this setting, progression-free survival data were encouraging, according to Jennifer A. Chan, MD, of Dana-Farber Cancer Institute, Boston.
“Vascular endothelial growth factor (VEGF) pathway inhibitors have shown activity in advanced neuroendocrine tumors. Recent studies have suggested that activation of the MET signaling pathway may also play a role in the growth of neuroendocrine tumors. Increased expression of MET correlates with decreased overall survival in pancreatic neuroendocrine tumors, Dr. Chan noted.”
“OMNI Health Media (OMNI) announces the launch of a new online community on CancerConnect for individuals with neuroendocrine tumors (NET). This community will provide patients and their loved ones with information and support. Join the conversation in the NET community here.
“Although neuroendocrine tumors have historically been considered rare, the incidence of neuroendocrine tumors has been increasing. Recent statistics suggest that the current number of people with neuroendocrine tumors exceeds 100,000 in the United States—more than the number of people with other, better known cancers like pancreatic or stomach cancer. The increase in NET diagnoses parallels improved diagnosis and treatments around the world.”
“In December 2016, the FDA informed Advanced Accelerator Applications that its new drug application for Lutathera (177Lutetium DOTA-octreotate) as a treatment for patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) would need to be resubmitted.
“The application was based on the phase III NETTER-1 trial, which randomized patients with advanced, progressive, somatostatin receptor-positive midgut NETS to receive either Lutathera (116 patients) plus best supportive care, including octreotide long-acting repeatable (LAR), or octreotide LAR alone (113 patients).”
“A group of doctors and other healthcare industry professionals have set out to develop a more efficient tool for assessing the true value of immuno-oncology (I/O) drugs. They note that these drugs often come with high prices that may distract from their advantages over other types of therapy. For example, Kroger Pharmacy is selling the checkpoint inhibitor ipilimumab (Yervoy) for $140 per mg. At the recommended dose of 3 mg/kg for melanoma patients, the total expense can be high. However, ipilimumab is one of the class of I/O drugs that have improved expectations on supportive care costs and survival benefit. The old measures of value may not apply. Therefore, how does one determine whether $140/mg is a fair price for the drug?”
“In a single-arm phase II study, cabozantinib demonstrated clinical activity in patients with advanced carcinoid and pancreatic neuroendocrine tumors (pNETs). Partial responses (PRs) were observed in 15% of each cohort treated with cabozantinib and stable disease was the best response in about two-thirds of patients.
“Median progression-free survival (PFS) exceeded 20 months in the pNET cohort and was >30 months in the carcinoid tumor cohort, said Jennifer A. Chan, MD, at the 2017 Gastrointestinal (GI) Cancers Symposium.”