Metastatic EGFRm+ Non-Small Cell Lung Cancer in the Era of Personalized Medicine

A diagnosis of lung cancer can be devastating, especially for those diagnosed with late-stage or metastatic disease. Thanks to scientific advances over the last 15 years, new treatment options are helping patients live longer than ever before. Personalized medicine has been at the heart of this progress, as researchers continue to discover new ways to target the cancer – and new strategies for treating all stages of this disease.

New developments in personalized medicine for metastatic epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) were highlighted at the 2018 European Society for Medical Oncology (ESMO) annual congress, which took place on October 19-23, in Munich, Germany. More than 20,000 participants from over 100 countries convened to discuss recent advances in diagnostics, biomarkers and genomics, which have dramatically improved outcomes for patients with lung cancer. AstraZeneca shared more than 50 presentations at the meeting, including new data from two clinical trials on acquired resistance in metastatic EGFRm+ NSCLC. We asked two of the researchers who led the trials – Dr. Suresh S. Ramalingam and Dr. Vassiliki Papadimitrakopoulou – to comment on the findings and discuss lung cancer treatment in the era of personalized medicine.

What is personalized medicine, and how does it relate to lung cancer?

 

Dr. Ramalingam: Personalized medicine in cancer is a treatment that is tailored to the specific genetics of a patient’s tumor. Until a few years ago, all patients with lung cancer received similar treatments, such as surgery, radiation or chemotherapy. Now we have the ability to study patients’ tumors in depth and select a treatment plan that is more likely to work for that person. This is a reality for non-small cell lung cancer, which represents nearly 85 percent of all lung cancer cases.


Dr. Papadimitrakopoulou: Personalized medicine is a treatment that is matched to the patient’s distinct tumor profile – usually mutations or other genomic alterations found in cancer cells. There are several examples of personalized medicine in lung cancer, including EGFR-targeted therapy for patients whose tumor cells have EGFR mutations. These therapies have completely changed the treatment landscape for lung cancer over the last ten years.


What is EGFR mutation? Why is it important?

Dr. Papadimitrakopoulou: EGFR is a protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found to be mutated in many lung cancer patients. Luckily, EGFR mutations are one of the most common targetable genetic alterations with treatment options readily available, which is why it’s so important for patients to have a full diagnosis that includes mutation testing.

At ESMO, you presented data about treatment resistance in EGFRm+ lung cancer. What does resistance mean? What does the data mean for patients?

Dr. Ramalingam: We know that most tumor cells eventually learn to bypass the way the treatment is preventing them from growing, and they become resistant. Treatment resistance inevitably limits the effectiveness of these therapies. Knowing how this happens can inform how we approach treatment going forward.

Our study found the two most frequent potential causes of resistance to EGFR-targeted therapy in patients who had only been treated with the first-line medicine. The data provide insights that will allow scientists to further study potential new treatment strategies to address the next stage of disease after the first therapy stops working.

What should patients know about mutation/biomarker testing, and what questions should they ask their doctor?

Dr. Ramalingam: For patients with metastatic lung cancer, we can determine the optimal treatment options based on the mutation status of their tumor. Treatment plans that do not factor in these mutations, or “biomarkers,” are less likely to be successful; the standard of care is to complete biomarker testing before initiating therapy.

Dr. Papadimitrakopoulou: Ideally, no patient with metastatic lung cancer should start therapy prior to tumor mutation testing. Patients should ask their doctor for information about getting a tissue biopsy or liquid biopsy to identify specific mutations. Usually the waiting period for results does not exceed two weeks.

What advice would you give to a patient who has just been diagnosed with lung cancer?

Dr. Ramalingam: Patients facing this difficult journey have more reasons to be hopeful now than ever before. Personalized medicine provides specific approaches with high likelihood of success for patients and helps care teams identify the optimal treatment approach for a given patient.

Dr. Papadimitrakopoulou: Patients with metastatic lung cancer should know that therapy should not be started without appropriate mutation testing.

 

Suresh S. Ramalingam, MD, is Deputy Director, Winship Cancer Institute at Emory University School in Atlanta.

Vassiliki A. Papadimitrakopoulou, MD, is Professor of Medicine, Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center.