Adjuvant Osimertinib and Advanced EGFR-Mutated NSCLC | NEJM

Summary

A phase 3 clinical trial has shown that osimertinib, an EGFR tyrosine kinase inhibitor, significantly improves progression-free survival in patients with unresectable stage III non-small-cell lung cancer with EGFR mutations. The trial, involving 216 patients, demonstrated a median progression-free survival of 39.1 months for osimertinib versus 5.6 months for placebo. Although 36-month overall survival did not show a significant difference, the treatment reduced the risk of disease progression, with adverse events occurring in 35% of the osimertinib group. These findings are published on NEJM.org.

Takeaways

• 🚫 Patients with unresectable stage III non-small-cell lung cancer (NSCLC) and an EGFR mutation previously had no approved targeted treatments available.
• 💊 Osimertinib, an EGFR tyrosine kinase inhibitor, is a recommended adjuvant treatment for resected EGFR-mutated NSCLC but was being tested for unresectable cases in this trial.
• 🔬 The trial was a phase 3, randomized, double-blind, placebo-controlled study involving 216 patients with stage III disease.
• 📈 Patients were assigned in a 2-to-1 ratio to receive daily oral osimertinib or placebo, following chemoradiotherapy without progression.
• 📊 The primary endpoint, median progression-free survival, was significantly longer with osimertinib at 39.1 months compared to 5.6 months with placebo.
• 📉 Interim data showed no statistically significant difference in 36-month overall survival between the osimertinib and placebo groups.
• ⚠️ Adverse events of grade 3 or higher occurred in 35% of patients in the osimertinib group, compared to 12% in the placebo group.
• 🌐 Radiation pneumonitis was a common adverse event but was mostly mild or moderate in severity.
• 🎯 Osimertinib demonstrated an improvement in progression-free survival for patients with unresectable EGFR-mutated stage III NSCLC.
• 📚 Full trial results are available for further review at NEJM.org, providing comprehensive data on the study's findings.

Q & A

What is the current status of targeted treatments for unresectable stage III non-small-cell lung cancer with an EGFR mutation?

There are no approved targeted treatments available for patients with unresectable stage III non-small-cell lung cancer with an EGFR mutation.

What is the role of osimertinib in treating EGFR-mutated non-small-cell lung cancer?

Osimertinib is an EGFR tyrosine kinase inhibitor and is recommended as an adjuvant treatment for resected EGFR-mutated non-small-cell lung cancer.

What was the purpose of the new trial mentioned in the script?

The new trial aimed to assess the efficacy and safety of adjuvant osimertinib among patients with unresectable, EGFR-mutated advanced disease.

How was the trial designed to test the efficacy of osimertinib?

The trial was a phase 3, randomized, double-blind, placebo-controlled trial involving 216 patients with stage III disease.

What was the ratio of patients assigned to receive osimertinib versus placebo in the trial?

Patients were randomly assigned in a 2-to-1 ratio to receive daily oral osimertinib or placebo.

What was the primary endpoint of the trial?

The primary endpoint of the trial was median progression-free survival.

What were the results for median progression-free survival with osimertinib and placebo?

The median progression-free survival was 39.1 months with osimertinib and 5.6 months with placebo.

What was the interim data regarding the 36-month overall survival between the two groups?

According to interim data, the between-group difference in 36-month overall survival was not statistically significant.

What was the incidence of grade 3 or higher adverse events in the osimertinib and placebo groups?

Grade 3 or higher adverse events occurred in 35% of the patients in the osimertinib group and 12% of those in the placebo group.

Was radiation pneumonitis a common adverse event in the trial? If so, what was its severity?

Yes, radiation pneumonitis was common, but most cases were mild or moderate in severity.

What conclusion did the authors draw from the trial regarding osimertinib's impact on patients with unresectable EGFR-mutated stage III non-small-cell lung cancer?

The authors concluded that osimertinib improved progression-free survival among patients with unresectable EGFR-mutated stage III non-small-cell lung cancer.

Where can the full trial results be found?

The full trial results are available at NEJM.org.