Larotrectinib – A Novel Age and Tumor Agnostic Therapy for TRK Fusion-Positive Cancers

March 20th, 2018

Tumor genomic profiling enables the identification of specific genomic alterations and thereby can provide personalized treatment options with targeted therapies that are specific for those molecular targets. Next-Generation Sequencing (NGS) platforms or second-generation sequencing perform massively parallel sequencing, which allows sequencing of millions of fragments of DNA from a single sample. Recently reported genomic profiling studies performed in patients with advanced cancer suggest that actionable mutations are found in 20-40% of patients’ tumors.
Larotrectinib is a potent and highly selective small molecule inhibitor of three TRK proteins, Tropomyosin Receptor Kinase genes NTRK1, NTRK2, and NTRK3. In a phase I-II study involving children, adolescents and adults with 17 unique cancer diagnoses, the Overall Response Rate was 75% and at 1 year, 71% of the responses were ongoing and 55% of the patients remained progression-free. It was concluded from this study that TRK fusions defined a unique molecular subgroup of advanced solid tumors in children and adults and Larotrectinib had marked and durable antitumor activity in patients with TRK fusion-positive cancer, regardless of the age of the patient or tumor type.

Alcohol and Cancer: A Statement of the American Society of Clinical Oncology

November 17th, 2017

Alcohol consumption is an established risk factor for several malignancies, and is a potentially modifiable risk factor for cancer. The International Agency for Research on Cancer (IARC), a branch of WHO, classified alcohol as a group 1 carcinogen. The American Heart Association, American Cancer Society, and US Department of Health and Human Services all recommend that men limit intake to one to two drinks per day and women to one drink per day. People who do not currently drink alcohol should not start for any reason. There is a clear association between alcohol and upper aerodigestive tract cancers (larynx, esophagus, and oral cavity/pharynx). A recent meta-analysis of cohort studies among 209,597 cancer survivors showed an 8% increase in overall mortality and a 17% increased risk for recurrence in the highest versus lowest alcohol consumers. The benefit of alcohol consumption on cardiovascular health likely has been overstated and the net effect of alcohol is harmful. Alcohol consumption should therefore not be recommended to prevent cardiovascular disease or all-cause mortality.

FDA Approves First Biosimilar for Cancer Treatment

September 20th, 2017

The FDA on Sept. 14, 2017 approved MYASI® (Bevacizumab-awwb) as a Biosimilar to AVASTIN® (Bevacizumab). MYASI® is the first Biosimilar approved in the U.S. for the treatment of cancer. A Biosimilar must show that it has no clinically meaningful differences in terms of safety and effectiveness from the already approved biological product (also known as reference product). A Biosimilar product can only be approved by the FDA if it has the same mechanism of action, route of administration, dosage form and strength as the reference product, and only for the indications and conditions of use, that have been approved for the reference product. The approval of MYASI® was based on comparisons of extensive structural and functional product characterization, animal data, human PharmacoKinetic and pharmacodynamic data, clinical immunogenicity, between MYASI® and AVASTIN® (Bevacizumab), and it was noted that MYASI® is highly similar to AVASTIN® and that there are no clinically meaningful differences between the two products.

FDA’s First Tissue/Site-Agnostic Approval

July 26th, 2017

The FDA for the first time approved a cancer treatment based on specific genetic biomarker, rather than location in the body where the tumor originated. KEYTRUDA®, an anti-PD1 monoclonal antibody was granted accelerated approval for treatment of adult and pediatric patients with unresectable or metastatic, MicroSatellite Instability-High (MSI-H) or MisMatch Repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options or with MSI-H or dMMR ColoRectal Cancer that has progressed following treatment with a Fluoropyrimidine, Oxaliplatin, and Irinotecan. MMR gene deficiency can be detected by ImmunoHistoChemistry and MSI testing is performed using a PCR based assay.

New Biomarker to predict Cancer Recurrence or Metastasis

March 23rd, 2011

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.

Environment and Cancer

March 7th, 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.

Oncoprescribe Blog: Identifying the Origin of Challenging Tumors

December 14th, 2010

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.