Trial results for the Phase 2 APPLE study (NCT02856893) investigating different strategies for delivering osimertinib in EGFR T790M plasma positive NSCLC patients were posted on ClinicalTrials.gov on 2025-10-31. The study found that a sequential treatment strategy of gefitinib until progression, followed by osimertinib based on blood test monitoring, resulted in an 18-month progression-free survival (PFS) rate of 67.2%.
Background
The APPLE trial (Osimertinib Treatment on EGFR T790M Plasma Positive NSCLC Patients) aimed to evaluate optimal strategies for administering osimertinib in advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. Specifically, it focused on those with EGFR T790M plasma positive status.
Trial design
The APPLE study (NCT02856893) was a Phase 2 trial that enrolled 156 participants with NSCLC. The trial investigated different treatment sequences involving osimertinib and gefitinib. The study compared three main strategies: osimertinib administered until progression; gefitinib administered until progression, followed by osimertinib based on positive blood test for T790M mutation or radiological progression; and gefitinib administered until progression, followed by osimertinib.
Key results
The trial evaluated several key outcomes comparing the different treatment strategies. For the "PFS Rate at 18 Months":
- The Osimertinib Till Progression group showed a PFS rate of 51.1% (84% Confidence Interval).
- The Gefitinib Till + Blood Test/Progression Than Osimertinib group achieved a PFS rate of 67.2% (84% Confidence Interval).
- The Gefitinib Till Progression Than Osimertinib group had a PFS rate of 53.5% (84% Confidence Interval).
Regarding "PFS While Receiving Osimertinib by RECIST Criteria 1.1":
- The median PFS for the Osimertinib Till Progression group was 19.48 months (95% Confidence Interval).
- The median PFS for the Gefitinib Till + Blood Test/Progression Than Osimertinib group was 21.98 months (95% Confidence Interval).
- The median PFS for the Gefitinib Till Progression Than Osimertinib group was 20.17 months (95% Confidence Interval).
The "Overall Response Rate (ORR) to Osimertinib" was 0.889 (95% Confidence Interval) for the Osimertinib Till Progression group and 0.656 (95% Confidence Interval) for the Gefitinib Till + Blood Test/Progression Than Osimertinib group.
What this means
The results from the APPLE trial suggest that a sequential treatment approach, where gefitinib is administered first and then followed by osimertinib based on blood test monitoring for T790M mutation or radiological progression, may offer a more favorable progression-free survival outcome compared to upfront osimertinib or sequential gefitinib followed by osimertinib without blood test guidance. The higher 18-month PFS rate and extended median PFS in the blood test-guided sequential arm indicate a potential benefit for this strategy in EGFR T790M plasma positive NSCLC patients.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT02856893, titled "Osimertinib Treatment on EGFR T790M Plasma Positive NSCLC Patients (APPLE)," were posted on 2025-10-31 on clinicaltrials.gov.