“Cabozantinib (Cabometyx) demonstrated promising clinical activity in patients with carcinoid tumors and pancreatic neuroendocrine tumors (NETs) in a phase II trial.
“Patients with advanced carcinoid tumors (n = 41) or pancreatic NETs (n = 20) were enrolled in parallel cohorts. Both groups received 60 mg of oral cabozantinib daily and were restaged every 2 months for the first 6 months, and then every 3 months.”
Diagnosis of adenocarcinoma of the lung, a major subtype of non-small lung cancer (NSCLC), nowadays triggers mandatory testing of tumor tissue for alterations in four genes: EGFR, ALK, ROS1, and more recently, BRAF. If present, these alterations predict sensitivity to specific targeted drugs approved by the U.S. Food and Drug Administration (FDA) that work better and often longer than standard chemotherapy, and are better tolerated.
However, there are many more targetable/actionable genomic alterations (also known as “drivers”) in NSCLC. This blog post will briefly discuss most of them, with the goal of promoting molecular testing for more than the four “usual suspects” mentioned above. Some patients with these alterations may benefit from FDA-approved drugs or from enrollment in clinical trials that are testing additional drugs and drug combinations. Continue reading…
“Treatment with cabozantinib was tied to objective tumor responses and promising progression-free survival (PFS) in patients with advanced carcinoid and pancreatic neuroendocrine tumors (pNET), researchers reported here.
“With a daily cabozantinib (Cabometyx, Cometriq) treatment, 15% of 20 patients with pNET achieved partial response (95% CI 5-36%) and 75% achieved stable disease (95% CI 53-89%), which was the the trial’s primary endpoint, according to Jennifer Chan, MD, MPH, of the Dana-Farber Cancer Institute in Boston, and colleagues.”
“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.”
“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.”
“Treatment with the multikinase inhibitor cabozantinib (Cabometyx) alone or with erlotinib (Tarceva) improved progression-free survival vs erlotinib alone in second- or third-line treatment of advanced nonsquamous epidermal growth factor receptor (EGFR) wild-type non–small cell lung cancer (NSCLC), according to the phase II ECOG-ACRIN 1512 trial reported by Neal et al in The Lancet Oncology.”
“A recently published international clinical Phase III trial of a promising drug for treating advanced prostate cancer ended with surprising results: the new therapeutic agent failed to achieve any significant improvement in the overall survival of patients compared with the established standard treatment. This and other data from the study have now been published in the leading magazine Journal of Clinical Oncology. Researchers from MedUni Vienna played a significant part in the study. The study was coordinated by the recently nominated ‘best hospital’ in the USA, Massachusetts General Hospital (MGH) of Harvard Medical School.”
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“Exelixis, Inc. EXEL, +9.21% today announced positive results from a phase 2 clinical study evaluating cabozantinib as a treatment for EGFR wild-type non-small cell lung cancer (NSCLC). The trial, Study E1512, is a randomized phase 2 trial by the ECOG-ACRIN Cancer Research Group of cabozantinib and erlotinib, alone or in combination, as second- or third-line therapy in patients with metastatic EGFR wild-type NSCLC. Exelixis previously announced positive top-line results from this trial in November 2014. Data from the trial will be presented today during an oral presentation (Abstract #8003) at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO), which is being held this week in Chicago, Illinois. Study chair Joel Neal, M.D., Ph.D., of ECOG-ACRIN’s Thoracic Cancer Committee and an Assistant Professor of Medicine (Oncology) at Stanford University/Stanford Cancer Institute will present the results.
“Study E1512 met its primary endpoint, demonstrating significant increases in progression-free survival (PFS) for cabozantinib and the combination of cabozantinib plus erlotinib when individually compared to the erlotinib arm. The median PFS for the combination of cabozantinib and erlotinib was 4.7 months versus 1.9 months for erlotinib alone, a more than two-fold increase that corresponds to a 65% reduction in the risk of disease worsening (hazard ratio [HR]=0.35, 80% CI 0.23-0.52, p=0.0005). The median PFS for cabozantinib monotherapy was 4.2 months versus 1.9 months for erlotinib alone, a more than doubling that corresponds to a 62% reduction in the risk of disease worsening (HR=0.38, 80% CI 0.27-0.55, p=0.0004).”
The gist: A drug called cabozantinib doesn’t do any better than a steroid treatment when it comes to relieving bone pain in men with metastatic castration-resistant prostate cancer. That was the conclusion of a recent clinical trial that tested the drug in volunteer patients. The trial enrolled men who were suffering from moderate to severe pain despite optimized narcotic medication, and whose cancer had worsened after treatment with docetaxel as well as abiraterone and/or enzalutamide. Some of the men in the trial were treated with cabozantinib, and some with the steroid treatment mitoxantrone/prednisone.
“Exelixis (EXEL) announced Monday that treatment with cabozantinib failed to alleviate bone pain compared to a steroid control in men with advanced, metastatic prostate cancer. A negative outcome from the so-called COMET-2 prostate cancer study of cabozantinib was widely expected given the previously announced failure of the COMET-1 study in September. Still, Exelixis shares fell another 10% to $1.49 — an all-time low — on heightened concerns that ongoing cabozantinib studies in kidney and liver cancer may also prove disappointing.
“A few years ago, there was much optimism for cabozantinib based on phase II data showing the drug cleared bone lesions and reduced pain in advanced prostate cancer patients. Cancer that metastasizes, or spreads, to bones is a serious complication leading to fractures, increased pain and eventual death. While many cancer drugs can shrink or eliminate tumors in soft tissue, few if any had ever demonstrated an ability to clear up bone metastases.
“All too often, promising results from phase II studies don’t pan out when larger, confirmatory phase III studies are conducted. That’s exactly what happened to Exelixis. In the COMET-2 study, 15% of prostate cancer patients with moderate to severe bone pain despite use of narcotics responded to treatment with cabozantinib compared to 17% of patients treated with steroids. Clearly, this is not the results Exelixis had in mind three years ago when reporting on the phase II bone lesion/bone pain data in the phase II study.”