How to Overcome Drug Resistance to Target Therapy in Non Small Cell Lung Cancer?--Dr. Leona Horn's Interview at NCCN 2015

Reproduced from Oncology Frontier

Leona Horn, MD, MSc. Associate Professor
Assistant Director, Educational Development Program
Medical Director, Thoracic Oncology Program
Department of Medicine, Vanderbilt University
Photo at NCCN annual meeting , Hollywood, FL 

Oncology Frontier: How do we overcome the problem of drug resistance to Target Therapy in the treatment of NSCLC?

Dr Horn: This is an issue we are all trying to deal with explore.

One of the key issues is re-biopsying patients when they are on targeted therapies, for example, and their disease is progressing.

Through the biopsies, we are able to see the mechanism of acquired resistance to the targeted therapies and that is helping us guide future therapies.

An example is in the EGFR mutation-positive patient population, we know that about 50% of those patients will have T790M as their mechanism of acquired resistance.

Now we have third-generation EGFR inhibitors that are specifically targeting those this patient population with impressive results so far.

What everyone is doing, including at Vanderbilt University, is that when these patients are progressing on the third-generation inhibitors, we are doing additional biopsies so we can look for new mechanisms of acquired resistance and develop new therapies for lung cancer patients.

What is the optimal therapy for leptomeningeal disease in non-small cell lung cancer patients?

Dr Horn: We don’t know what the best treatments are for patients with leptomeningeal disease. There is some interesting data with a the second-generation ALK inhibitors including with ceritinib, alectinib and X396 where we are seeing CNS responses, probably due to better drug penetration than what is seen with crizotinib.

But we know that about 30-50% of patients on targeted therapies will develop brain metastases as their site of progression.

There was some data several years ago showing pulse doses of high-dose erlotinib given at 1500mg rather than 150 mg once a week could help in patients with leptomeningeal disease or CNS disease, but we still don’t have great treatment options for these patients.

And right now, radiation treatment is standard of care. Unfortunately, we know from many of these patients that the prognosis is poor.

As a member of the NCCN lung cancer guidelines panel, could you comment on the recently updated guidelines that relate to non-small cell lung cancer?

Dr Horn: The guidelines seem to be changing on a monthly basis.

Ceritinib was added as an option for patients with acquired resistance to crizotinib for ALK-positive non-small cell lung cancer patients.

We will likely be adding nivolumab as third-line treatment and beyond for patients with squamous cell lung cancer.

As new treatments emerge and new drugs are developed, the guidelines will continue to be updated. There were no other major changes in terms of therapeutic options at the first iteration, but to put it into perspective of where we are, it is 2015 and they are already on their fifth amendment to the guidelines.

So the updates are constant as new data becomes available. We have our panel annual meeting coming up in July when we really meet in person and work through some of the specific details for the NCCN Guidelines.

Reference:

[NCCN 2015] 非小细胞肺癌：NCCN指南更新 克服靶向治疗耐药方法 2015-03-15 L.Horn © 肿瘤瞭望 © 微信公众号