FDA to Regulate Personalized Medicine

Now that medical treatment is increasingly tailored to patient subtypes (eg, lung cancer patients with mutations in the ALK gene can be treated with Xalkori), the U.S. Food and Drug Administration (FDA) has released a new report explaining how it will regulate personalized therapies and tests. The first targeted therapy used in the U.S. was trastuzumab, which is for HER2 breast cancer and was approved in 1998. Since then, the FDA has approved more than 100 treatments that target specific genetic abnormalities, including four drugs for cancer subtypes that are identified by companion test kits.


FDA to Regulate Personalized Medicine

Now that medical treatment is increasingly tailored to patient subtypes (eg, lung cancer patients with mutations in the ALK gene can be treated with Xalkori), the U.S. Food and Drug Administration (FDA) has released a new report explaining how it will regulate personalized therapies and tests. The first targeted therapy used in the U.S. was trastuzumab, which is for HER2 breast cancer and was approved in 1998. Since then, the FDA has approved more than 100 treatments that target specific genetic abnormalities, including four drugs for cancer subtypes that are identified by companion test kits.


Clinical Response to a Lapatinib-Based Therapy of a Li-Fraumeni Syndrome Patient with a Novel HER2-V659E Mutation

“Genomic characterization of recurrent breast and lung tumors developed over the course of 10 years in a 29-year-old patient with a germline p53 mutation (Li-Fraumeni Syndrome) identified oncogenic alterations in the HER2 and EGFR genes across all tumors, including HER2 amplifications, an EGFR-exon 20 insertion, and the first-in-human HER2-V659E mutation showing a phenotypic convergent evolution towards HER2 and EGFR alterations. Following the identification of HER2-activating events in the most recent lung carcinoma and in circulating tumor cells, we treated the reminiscent metastatic lesions with a lapatinib-based therapy. A clinical response both symptomatic and radiologic was achieved. HER2-V659E sensitivity to lapatinib was confirmed in the laboratory.”


Safer, Peptide-Based Therapies Studied as Alternative to Monoclonal Antibodies

Monoclonal antibodies and small-molecule inhibitors have been the primary treatment methods for many types of cancer for many years, but new studies may change that. Peptides, proteins made of small chains of 10 to 50 amino acids, are being examined as possible cost-effective, more successful, safer anticancer vaccines. Researchers have identified two regions on the HER1 (also known as the EGFR) protein as possible targets for these peptide-based drugs. These agents could be used in the treatment of lung cancer, breast cancer, colorectal cancer, and head and neck cancers. If successful, the EGFR-targeting peptide vaccines could be combined with immunotherapies for the HER2 and VEGF proteins, possibly reducing the likelihood that the cancer will develop resistance to the treatment, a common pitfall of monoclonal antibody drugs such as cetuximab (Erbitux).


Biomarker-Guided Targeted Therapy Is Becoming a Reality

A massive database study performed recently in France demonstrates that genetic testing of non-small cell lung cancer (NSCLC) tumors for disease-relevant biomarkers is feasible, and indeed already helps guide treatment strategies for patients. France’s National Cancer Institute funds routine assessment of genetic alterations in six genes for NSCLC patients: EGFR, KRAS, ALK, BRAF, HER2, and PI3K. Since April 2012, these genetic analyses have been collected into a database. By now, biomarker assessments have been performed for 10,000 NSCLC patients. Of the patients for whom treatment data was available, over half received therapies guided directly by their biomarker testing profile. For example, over half of patients who were found to have a mutation in the EGFR gene were treated with EGFR inhibitors. As the database continues to grow, researchers recommend that newer biomarkers, like the ROS1 gene, should be added to the analysis. Furthermore, they urge that the availability of clinical trials of biomarker-targeted treatments needs to be increased.


First-in-Human Phase I Dose-Escalation Study of the HSP90 Inhibitor AUY922 in Patients with Advanced Solid Tumors

A phase I study was conducted with the primary objective of determining the maximum tolerated dose (MTD) of AUY922 in patients with advanced solid tumors. Secondary objectives included characterization of the safety, pharmacokinetic, and pharmacodynamic profiles. At the recommended phase II dose of 70 mg/m2, AUY922 exhibited acceptable tolerability, and phase II single-agent and combination studies have been initiated in patients with HER2-positive breast, gastric, and non–small cell lung cancers.


Lung Cancer That Harbors a HER2 Mutation: Epidemiologic Characteristics and Therapeutic Perspectives

HER2 mutations are identified in approximately 2%of non–small-cell lung cancers (NSCLC). There are few data available that describe the clinical course of patients with HER2-mutated NSCLC.

This study, the largest to date dedicated to HER2-mutated NSCLC, reinforces the importance of screening for HER2 mutations in lung adenocarcinomas and suggests the potential efficacy of HER2-targeted drugs in this population.


PUMA and BIM Are Required for Oncogene Inactivation-Induced Apoptosis

The clinical efficacy of tyrosine kinase inhibitors supports the dependence of distinct subsets of cancers on specific driver mutations for survival, a phenomenon called “oncogene addiction.” We demonstrate that PUMA and BIM are the key apoptotic effectors of tyrosine kinase inhibitors in breast cancers with amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) and lung cancers with epidermal growth factor receptor (EGFR) mutants…”