The FDA on August 30, 2012 granted accelerated approval for AFINITOR® (Everolimus) for the treatment of pediatric and adult patients with tuberous sclerosis complex (TSC) who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. AFINITOR® tablets for oral suspension (AFINITOR® Disperz) is a product of Novartis Pharmaceuticals Corp.
SUMMARY:Durable tumor responses have been demonstrated in previous clinical studies using high dose interleukin 2 and anti-CTLA 4 antibody YERVOY® (Ipilimumab), for advanced malignancies such as metastatic melanoma. The programmed death 1 (PD-1) receptor is an inhibitory receptor expressed on activated T-cells in the tumor micro environment. It has two known ligands, PD-L1 and PD-L2 which can turn off the immune system when they combine with the PD-1 receptor. BMS-936558 is an anti-PD-1 targeted, fully human, monoclonal antibody which acts similar to the anti CTLA 4 antibody YERVOY®, thereby unleashing the T cell response against cancer cells. Results from a Phase 1 study in which 296 patients were enrolled demonstrated a durable response rate of 18% among patients with advanced non- small cell lung cancer, 28% among patients with advanced melanoma and 27% among patients with advanced renal cell carcinoma. PD-L1 was identified as a potential biomarker for response, with no responses seen in PD-L1 negative tumors. Topalian SL, Hodi S, Brahmer JR, et al. NEJM June 2, 2012.
OncoPrescribe LLC published their first newsletter on metastatic lung cancer. The title of the article is “Improving Survival for Patients with Advanced Non−Small-Cell Lung Cancer”. This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of A. Webb Roberts Center for CME of Baylor Health Care System and Oncoprescribe, LLC. A. Webb Roberts Center for CME of Baylor Health Care System is accredited by the ACCME to provide continuing medical education for physicians.
Oncoprescribe is a comprehensive Web-Based Resource for Oncologists, Nurses, Nurse Practitioners, Physician Assistants and Pharmacists. OncoPrescribe is regularly updated by our Oncology professionals who scour the published literature – and constantly attend conferences at which the latest research findings are presented.
With OncoPrescribe, you’ll probably see regimens available for specific diagnoses and stages that you didn’t even know about, and you’ll be able to prescribe that regimen with confidence because you’ll know there’s a corresponding reference, too.
So, what are you waiting for? Check it out. You will love it
A protein variant of carboxypeptidase E has now been shown to induce tumor growth and metastases. By measuring the level of this protein in the tumor and surrounding tissue, we may soon be able to predict whether a tumor is likely to spread or has already spread. The predictability of tumor behavior, using this new novel biomarker, appears to trump the outcomes based on staging and grade of the tumor. The tempo of the disease even in patients with advanced cancer can be predicted measuring the levels of this biomarker, with tumors expressing high levels of this protein doing poorly. This may also help the clinician determine when to treat a patient with cancer and when to just monitor without pursuing aggressive chemotherapeutic intervention.
These findings were published in the Journal of Clinical Investigation, Feb 2011.
More than a third of Americans will develop some form of cancer during their life time. Interestingly 80-90% of the cancers in the western hemisphere has been attributed to environmental factors. With cancer being the second common cause of mortality in the USA, prevention of cancer related morbidity and mortality can be accomplished by avoiding environmental pollution with carcinogens and eliminating exposure to existing carcinogenic agents in the environment. This sentiment was eloquently verbalized by Dr. David Christiani in the March 3, 2011 issue of the NEJM.
Despite the progress made in cancer treatment and Genomics, we cannot lose sight of the fact that prevention is better than cure.
Cancer of Unknown Primary Site (CUPS) may soon become a term of the past. With the availability of microarray technology, gene expression patterns of metastatic poorly differentiated and undifferentiated cancers can now be compared with gene expression patterns of known tissue types representing morphology of solid tumors. This in turn may help identify the site of origin of a particular tumor.
The “Tissue of Origin”is one such test cleared by the FDA to identify the origin of a challenging tumor. It is encouraging to note that these molecular methodologies are helping both diagnose and treat cancer patients.
Denosumab (Xgeva) was approved by the FDA for the prevention of Skeletal Related Events (SRE’s) in patients with bone metastases from solid tumors. Denosumab is a monoclonal antibody targeting a protein called RANKL (Receptor Activator for Nuclear Factor kappa B Ligand). RANKL also known as ODF (osteoclast differentiation factor) is an important molecule necessary for maintaining bone homeostasis. Overproduction of RANKL leads to increased osteoclastic activity resulting in bone resorption. Accelerated bone resorption can not only result in osteoporosis, but has also been implicated in the development of tumor related bone metastases. Denosumab binds to RANKL negating the formation, function and survival of osteoclasts.
Two international randomized studies demonstrated the superiority of Denosumab over Zoledronic acid in patients with bone metastases, secondary to Breast Cancer and Castrate Resistant Prostate Cancer. In a third study involving patients with other solid tumors with bone metastases, Denosumab was found to be non-inferior to Zoledronic acid.
The role of Bevacizumab in combination with chemotherapy for patients with advanced Non Small Cell Lung Cancer is well established. However the safety of Bevacizumab in this patient population with brain metastases has been unclear with the potential risk of CNS bleed. This issue was addressed in the PASSPORT trial which enrolled nonsquamous histology Non Small Cell Lung Cancer patients with treated brain metastases. The addition of bevacizumab to conventional chemotherapy or erlotinib in this trial was associated with a low incidence of CNS bleed suggesting that bevacizumab could be safely given for patients with Non Small Cell Lung Cancer with treated brain metastases.
How do mutations and overexpression of certain oncogenes impact treatment decisions? So, Here is an answer the Oncoprescribe way.
If a patient with colon cancer has a tumor with KRAS mutation Erbitux or Vectibix ( EGFR targeted monoclonal antibodies ) will not work.
However if a patient with Non Small Cell Lung Cancer has a tumor with mutations involving exon 19 or exon 21, small molecule Tyrosine Kinase Inhibitors such as Tarceva (Erlotinib) may be more effective than chemotherapy.
Tumors in patients with Non Small Cell Lung Cancer with high ERCC 1 gene expression are resistant to platinum compounds and non-platinum combination regimens should be a serious consideration.