The primary completion of a Phase 3 study evaluating osimertinib (Tagrisso) in combination with chemotherapy for non-small cell lung cancer (NSCLC) was announced on 2024-10-28. The trial demonstrated that the combination therapy significantly extended median progression-free survival (PFS) to 8.4 months compared to 4.4 months for chemotherapy plus placebo. Median overall survival (OS) also showed improvement, reaching 15.9 months versus 9.8 months.

Background

The Phase 3 study investigated osimertinib in combination with chemotherapy for patients with non-small cell lung cancer (NSCLC). Specifically, it focused on patients whose disease had progressed extracranially after receiving first-line osimertinib treatment.

Trial design

The Phase 3 study, NCT04765059, enrolled 98 participants with non-small cell lung cancer whose disease had progressed extracranially following first-line osimertinib treatment. It compared osimertinib plus chemotherapy (pemetrexed and cisplatin or carboplatin) against placebo plus the same chemotherapy regimen. Key outcomes measured included Progression Free Survival (PFS), Intracranial Progression Free Survival, Extracranial Progression Free Survival, and Overall Survival (OS).

Key results

The trial reported a median Progression Free Survival (PFS) of 8.4 Months for the osimertinib plus chemotherapy arm, compared to 4.4 Months for the placebo plus chemotherapy arm. The efficacy comparison yielded a Hazard Ratio (HR) of 0.43 (95% Confidence Interval: 0.27-0.7).

Median Overall Survival (OS) was 15.9 Months in the osimertinib plus chemotherapy arm versus 9.8 Months in the placebo plus chemotherapy arm, with an HR of 0.71 (95% Confidence Interval: 0.42-1.23).

Intracranial Progression Free Survival was also assessed. In participants with brain metastases at baseline, 81.8 Percentage of participants in the osimertinib arm achieved this outcome compared to 55.6 Percentage of participants in the placebo arm (HR: 0.56; 95% CI: 0.27-1.13). For those without brain metastases at baseline, the figures were 86.7 Percentage of participants for the osimertinib arm and 63.1 Percentage of participants for the placebo arm (HR: 0.43; 95% CI: 0.26-0.71).

Extracranial Progression Free Survival showed a median of 8.4 Months for the osimertinib arm and 5.2 Months for the placebo arm.

What this means

This Phase 3 trial indicates that combining osimertinib with chemotherapy provides a clinical benefit for patients with non-small cell lung cancer whose disease progressed after initial osimertinib treatment. The improvements in median Progression Free Survival, Overall Survival, and Intracranial Progression Free Survival suggest a new treatment option for this patient population.

Source

These trial results were posted on ClinicalTrials.gov on 2024-10-28. The full details of the study, NCT04765059, are available on clinicaltrials.gov.