Treatment of Lung Cancer: A Paradigm Shift

Over the past few years, a major shift has been taking place in the treatment of lung cancer (and in other cancers), guided by developments in genomic research. “One-size-fits-all” standard chemotherapies are being replaced by or combined with immunotherapies and targeted agents based on the molecular profile of the tumor. At present, the Food and Drug Administration has approved these novel therapies for the following gene aberrations in lung cancer: EGFR, ALK, ROS-1, BRAF v600e, NTRK, MET and RET. Several other gene targets (KRAS, HER2, NRG1 fusions, atypical EGFR mutations) are under investigation to result in an even greater division of lung cancer types that will have personalized therapeutic interventions to address the gene abnormalities.

The significant impact of lung cancer, with more than 228,000 Americans diagnosed this year, and 135,720 people dying of lung cancer, requires accelerating the appropriate use of novel therapeutics through next generation sequencing of lung tumors to define targets for treatment options to extend and/or improve quality of life.

Paul A. Bunn, Jr, MD Distinguished Professor and Dudley Endowed Chair, University of Colorado Cancer Center and member of VieCure’s Clinical Advisory Council has stated, “Recent data shows that patients diagnosed with lung cancer have longer survival than in recent years and for a significant portion the improved therapies are oral with better survival and less toxicity compare to chemotherapy. This is due in part to genomic testing to identify the one third of patients who have gene alterations that can be targeted with novel oral therapies and/or immunotherapies. Thus, all lung cancer patients should have this testing performed before initiation of therapy.”

During a recent presentation to VieCure’s Clinical Advisory Council, Dr. Bunn highlighted the importance of genomic sequencing and the recent advancements that have been made to prolong patient survivorship and improve quality of life.

Oncologists are moving away from standard chemotherapy to approved, precision therapies

The survival rates and quality of life for both men and women who have been diagnosed with lung cancer have improved over the past several years, due to improvements in screening and advancements in treatment, especially the transition to genomics-based testing and precision medicine. There are an increasing number of approved drugs to help treat a patient’s specific driver gene to help treat patients and prevent further spread of cancer.

Research has increasingly demonstrated the importance of a patient's tumor profile to identify drivers

At present we have approved therapies for seven known driver genes; however, continuing research will identify other targets and therapeutics will be developed for these so that we can do even better for patients. For those who do not have a genomic alteration, immunotherapy is being used in some cases as the first line of therapy. Combination therapies (chemotherapy, immunotherapy, and/or targeted therapies) in the neoadjuvant setting may be shown to be important, allowing for radiotherapy and/or surgical interventions to cure more disease.

FDA Apporved Agents and drug discovery continue to escalate

The table below shows which gene alterations have FDA approved therapies. The rapid drug approvals and numerous genomic alterations, tumor markers and combinations put pressure on oncologists to ensure that they have adequate understanding and knowledge of a potential therapy– highlighting the need for precision oncology clinical decision support systems. These targeted therapies are prolonging patients’ life, sometimes for several years.

Clinicians are beginning to research mechanisms that emerge to mitigate the effects of these novel agents

Since these therapies are so new, it is imperative that clinicians learn about the effects and potential issues that patients may experience while on treatment. “Emerging research has shown,”, according to VieCure’s Chief Scientific Officer, Dr. Fred Ashbury, “that the toxicities associated with these novel therapies can behave differently compared to chemotherapies. These new behaviors, therefore, require disparate strategies for effective management so the patient can participate fully on the prescribed treatment to optimize outcomes.”

The promise of genomic-guided medicine is being realized in the Non-Small Cell Lung Cancer setting as well as other diseases

NSCLC as well as some other cancers (breast, colon, ovarian) have been on the forefront of genomics research in oncology. The advancement in next generation tumor sequence testing has produced vast amounts of data and knowledge that will further accelerate drug development.