Q&A: FDA approves new first-line treatment for patients with metastatic EGFR-mutated non-small cell lung cancer

Newly approved drug combination was tested in clinical trials led by UCLA researcher Dr. Edward Garon
Edward B. Garon, MD, MS
Edward B. Garon, MD, MS

A new drug regimen to treat advanced EGFR-mutated non-small cell lung cancer, the most common type of lung cancer among non-smokers, has been approved by the U.S. Food and Drug Administration (FDA) as a new first-line defense. Ramucirumab in combination with erlotinib is the first FDA-approved targeted combination of drugs for EGFR mutant non-small cell lung cancer. This combination works by blocking blood vessel formation along with the action of the EGFR protein.

This approval is based on the efficacy and safety seen in the global, randomized, placebo-controlled Phase 3 RELAY trial, where UCLA’s Dr. Edward Garon was the North America lead investigator. The results were recently published online in The Lancet Oncology. In this study, the combination treatment demonstrated a statistically significant and clinically meaningful improvement in progression-free survival – the time patients lived without their cancer growing or spreading after starting treatment – compared to the arm of the trial in which patients received erlotinib plus placebo, 19.4 months compared to 12.4 months.

Dr. Edward Garon, associate professor of medicine at the David Geffen School of Medicine at UCLA and director of the Signal Transduction and Therapeutics Program at the UCLA Jonsson Comprehensive Cancer Center breaks down the significance of the FDA approval and it what it means for patients diagnosed with this type of lung cancer.

How common is this type of lung cancer and what are the current treatment options?

EGFR mutation positive non-small cell lung cancer is the most common subset of lung cancer among non-smokers. It is seen in about 10% of lung cancer patients in the United States, but at a much higher frequency in East Asia. Asian Americans and women are more likely than others to have EGFR mutation positive lung cancer. Until this approval, the only targeted therapy approach that was approved was single agent inhibitions of the EGFR protein.

What’s the preclinical rationale for the RELAY study?

There is a wealth of pre-clinical data showing cross talk between the EGFR pathway and the VEGFR pathway (the pathway blocked by ramucirumab). This data further indicates that approaches that block blood vessel formation (the mechanism for ramucirumab) should be particularly effective in lung cancer patients whose tumors harbor an EGFR mutation.

How does this drug combination work?

Two important pathways are both blocked by this combination. Erlotinib blocks EGFR signaling while ramucirumab blocks VEGFR signaling.

How is this drug/treatment an improvement over past treatments for lung cancer?

EGFR directed therapy has been shown to be superior to chemotherapy in this patient population. This is the first targeted combination approved for this subset of disease, leading to a longer period of time prior to worsening of disease. The period of time until the middle patient had worsening of disease or death was increased from 12.4 months in the erlotinib plus placebo arm to 19.4 months in the erlotinib plus ramucirumab arm.

Should this change the way patients are treated?

As with any new treatment, physicians will discuss this as a potential treatment options among treatment naïve, advanced EGFR mutation positive lung cancer patients.

CYRAMZA (ramucirumab) is an antiangiogenic therapy, which was developed by Eli Lilly and Company. Dr. Garon was quoted in the press release from Eli Lilly addressing the FDA approval.