“Although checkpoint blockade immunotherapies have advanced rapidly in the treatment paradigm for patients with non–small cell lung cancer (NSCLC), interest in developing targeted therapies for this malignancy has remained high. Building on the success of molecularly targeted drugs aimed at relatively small subsets of patients, researchers are increasingly aiming at the MET oncogene.
“During the past several years, interest in MET activity has grown as investigators have considered it both as a biomarker and target for treatment, particularly since the focus on MET exon 14 skipping mutations has led to the development of several second-generation MET inhibitors, according to Balazs Halmos, MD, MS.”
The University of Texas MD Anderson Cancer Center | Jan 17, 2018
“A pair of targeted therapies given before and after surgery for melanoma produced at least a six-fold increase in time to progression compared to standard-of-care surgery for patients with stage 3 disease, researchers at The University of Texas MD Anderson Cancer Center report in Lancet Oncology. Patients who had no sign of disease at surgery after combination treatment did not progress to metastasis.
“Early results of the study comparing surgery to pre- and post-surgical treatment with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib were so strikingly positive that MD Anderson’s data safety monitoring board ordered the randomized, prospective phase II trial halted and changed to a single-arm using the combination.”
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…
“Smokers are less likely than non-smokers to have lung cancers caused by targetable genetic changes. But a study published this week in the journal Clinical Cancer Research shows that when they do, smokers benefit just as much as non-smokers from targeted treatments.
” ‘A smoker or former smoker with a targetable alteration has the same probability of benefitting from targeted therapy as a never-smoker with a targetable alteration,’ says Dara Aisner, PhD, investigator at the University of Colorado Cancer Center and molecular pathologist at CU School of Medicine.”
“Traditional neoadjuvant chemotherapy along with dual HER2-targeted blockade yielded significantly better response rates than a novel approach using HER2-targeted chemotherapy plus HER2-targeted blockade, according to a randomized phase III trial.
” ‘Despite the improvements in outcomes associated with HER2-directed therapy, approximately a quarter of patients who receive treatment for their early breast cancer remain at risk of relapse after 8–10 years, and around 15% will die within a decade,’ wrote study authors led by Sara A. Hurvitz, MD, of the David Geffen School of Medicine at the University of California, Los Angeles. A need for new strategies in this setting led the investigators to test a neoadjuvant regimen of the antibody–drug conjugate trastuzumab emtansine along with pertuzumab in comparison with traditional systemic chemotherapy along with trastuzumab plus pertuzumab.”
“Back-to-back discoveries from Cleveland Clinic demonstrate for the first time how a testosterone-related genetic abnormality can help predict individual patient responses to specific prostate cancer therapies.
“The studies, published in the October 12 issue of JAMA Oncology, suggest that men who inherit this variant would benefit from a personalized treatment plan that targets specific hormonal pathways.”
“The targeted therapy gefitinib appears more effective in preventing recurrence after lung cancer surgery than the standard of care, chemotherapy. In a phase III clinical trial, patients with epidermal growth factor receptor (EGFR)-positive, stage II-IIIA non-small cell lung cancer (NSCLC) who received gefitinib went about 10 months longer without recurrence than patients who received chemotherapy. The study will be presented at the upcoming 2017 ASCO Annual Meeting in Chicago.
” ‘Adjuvant gefitinib may ultimately be considered as an important option for stage II-IIIA lung cancer patients with an active EGFR mutation, and we may consider routine EGFR testing in this earlier stage of lung cancer,’ said lead study author Yi-Long Wu, MD, a director of the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China. ‘We intend to follow these patients until we can fully measure overall survival as opposed to disease-free survival, which just measures disease recurrence.’ ”
“Researchers at the University of Cincinnati (UC) College of Medicine are enrolling patients in a clinical trial looking at targeted gene therapies in patients with early stage lung cancer who have had surgery.
“This could help researchers gain insight into genetic targets that could aid in earlier intervention and better outcomes for patients.
” ‘Despite therapeutic advances in recent years, cancer remains the second leading cause of death in the United States, and effective new therapies are still desperately needed. Additionally, lung cancer is the leading cause of cancer deaths for women and for men,’ says Sandra Starnes, MD, Dr. John B. Flege Jr. Chair in Cardiothoracic Surgery, associate professor of surgery and co-director of the UC Cancer Institute’s Comprehensive Lung Cancer Center. ‘Targeted genetic therapy holds great promise for improved efficacy in treating patients. In this trial, researchers will evaluate the use of a newer targeted therapy for early stage lung cancer patients who have had surgery and completed post-operative chemotherapy.’ ”