Compared with other standard treatments, untreated patients with advanced non–small-cell lung cancer (NSCLC) who also have an EGFR mutation live longer when treated with osimertinib, according to a new study.
In the phase 3 FLAURA clinical trial, frontline treatment with osimertinib improved median overall survival (OS) by 6.8 months compared with erlotinib or gefitinib.
These results were presented at the 2019 European Society for Medical Oncology Congress in Barcelona by Suresh S. Ramalingam, MD.
A Few Definitions
The epidermal growth factor receptor (EGFR) is a protein found on the surface of both normal cells and cancer cells in the body. Mutations in EGFR can lead to overexpression of the protein, and when this protein becomes too active, it can lead to cancer growth. About 15% of people with lung cancer in the United States have an EGFR mutation.
But there is some good news. We now have medications available—tyrosine kinase inhibitors (TKIs) like osimertinib—that specifically target this protein in some cancer cells and stop the cells from growing.
Median OS is defined as the length of time from the start of cancer treatment that half of the patients in the trial are still alive. In a clinical trial, measuring the median OS is one way to see how well a new treatment works.
Significant Survival Improvement
The FLAURA trial enrolled 556 newly diagnosed patients with EGFR-positive locally advanced NSCLC (their cancer had spread only to nearby tissues or lymph nodes) or metastatic NSCLC (their cancer had spread to other parts of the body). Patients were then randomly assigned to 1 of 2 treatment arms.
The majority of the patients in the study were female nonsmokers, with a median age of 64 years. A total of 279 patients received daily oral osimertinib, and in the control group, 277 patients received a standard TKI (erlotinib or gefitinib).
The median OS in the osimertinib group was 38.6 months, compared with 31.8 months in the control group. For patients on osimertinib, this translated to a 20% reduction in the risk of dying.
After 2 years, OS rates were 74% with osimertinib and 59% in the control arm. After 3 years, 54% of patients on osimertinib were still alive, compared with 44% in the erlotinib/gefitinib group.
“Osimertinib resulted in an improvement in overall survival in both a clinically and statistically significant manner,” said Dr Ramalingam, from the Winship Cancer Institute of Emory University in Atlanta. “The overall survival result you see for the control group in this study is among the highest reported for EGFR-mutated patients. We believe this is attributable to the crossover of patients from the control group to receive osimertinib upon progression. And, even with that in play, we see a 6.8-month improvement in survival with osimertinib.”
In other words, this study allowed patients in the control group to join the osimertinib group for second-line therapy if their cancer started to progress. But even with this crossover of patients who had cancer progression, people in the new, larger osimertinib group still lived longer on average than the people in the control group.
Osimertinib’s Benefit Was Durable
At 36 months, 28% of patients remained on first-line treatment with osimertinib compared with only 9% remaining on erlotinib or gefitinib. And on average, it took a little over 2 years until patients on osimertinib needed a subsequent treatment, versus only 13.7 months with the comparator drugs.
Of the 180 patients in the comparator arm who received a first subsequent treatment, 85 crossed over to osimertinib. According to Dr Ramalingam, this means that the “best drug”—osimertinib—should be used as the first line of therapy in these patients.
Fewer High-Grade Side Effects
The patients who received osimertinib were on their treatment longer (median 20.7 months vs 11.5 months in the control arm), so they had more time to experience the side effects of treatment. Despite this, serious side effects (grade 3 or greater) were less common in osimertinib patients (18%) compared with those who received erlotinib or gefitinib (29%).
“Osimertinib was associated with a favorable and consistent toxicity profile, despite prolonged exposure,” said Dr Ramalingam. “The final OS analysis of FLAURA reinforces osimertinib as the standard of care for first-line treatment of patients with EGFR-mutant advanced NSCLC.”
This study enrolled 556 patients from 29 countries, and Dr Ramalingam took the time to personally thank those patients, as well as their families, after presenting these study results in Barcelona.
“In my mind, there is no greater responsibility than when patients place their hopes, aspirations, and lives in our hands,” he said. “I am excited that the new milestone accomplished with osimertinib in this trial will serve as the platform to build on in our efforts to improve the lives of patients with lung cancer.”
