Real-world China study backs osimertinib in EGFR-mutated lung cancer

A prospective study across 22 Chinese institutions found first-line osimertinib delivered real-world outcomes in EGFR-mutated advanced NSCLC that were close to clinical trial results, including for patients who would not have qualified for FLAURA. The data also show materially worse survival for patients with additional gene co-mutations, especially TP53, pointing to the need for broader genomic testing and possibly combination therapy.

Why it matters: - First-line osimertinib remains a strong standard option for most patients with EGFR-mutated advanced non-small cell lung cancer. - The study shows that real-world patients in China, including older and sicker patients, can still see meaningful benefit from the drug. - The findings also identify a higher-risk subgroup with additional gene co-mutations that may need treatment beyond monotherapy.

What happened: - Researchers from 22 institutions across China, led by Zhejiang University School of Medicine, reported results from the FLOURISH study in Cancer Biology & Medicine. - The prospective, multicenter, non-interventional study enrolled 481 treatment-naïve patients with locally advanced or metastatic EGFR-mutated NSCLC. - All patients received first-line osimertinib. - The median follow-up was 31.3 months.

The details: - Median time to treatment discontinuation was 24.6 months. - Median real-world progression-free survival was 19.4 months. - The real-world progression-free survival result was close to the 18.9-month progression-free survival seen in the FLAURA trial. - The FLOURISH cohort included a higher share of patients with central nervous system metastases, at 34.3% versus 20.8% in FLAURA. - The cohort also included patients with poorer performance status than typical trial populations. - Overall survival reached 41.0 months. - 33.1% of patients were FLAURA-ineligible, mainly because of comorbidities or ECOG performance status of 2 or higher. - Even in that ineligible group, median overall survival was 33.5 months. - Baseline next-generation sequencing was performed in 118 patients. - Among sequenced patients, 76.3% had additional gene co-mutations in genes including TP53, HER2, KRAS, BRAF, ROS1, ALK, RB1, or PTEN. - Patients with co-mutations had median overall survival of 29.3 months, compared with not reached in patients with EGFR mutations alone. - TP53 co-mutations were present in 67.8% of sequenced patients. - Patients with TP53 co-mutations had median overall survival of 28.5 months, versus not reached in patients without TP53 alterations. - Safety was manageable, with 71.7% of patients experiencing any adverse event. - Grade 3 or higher adverse events occurred in 11.4% of patients. - The study reported no new safety signals.

Between the lines: - The study narrows a common gap between clinical trial data and routine practice by showing that osimertinib performance in China tracks closely with pivotal trial outcomes. - The survival penalty tied to co-mutations, especially TP53, suggests some patients may be biologically less responsive to single-agent osimertinib. - That pattern supports earlier use of comprehensive genomic profiling at diagnosis to find patients who may need more intensive treatment. - The authors said patients with additional gene mutations may need combination approaches from the start rather than single-agent therapy. - Recent studies such as FLAURA2 and MARIPOSA have reported improved outcomes with combination regimens in patients with TP53 co-mutations. - The ongoing TOP study is evaluating osimertinib plus chemotherapy in this higher-risk population.

What's next: - Clinicians are likely to use these results to support broader genomic testing before starting treatment. - More patients with co-mutations may be steered toward combination strategies or closer monitoring. - The TOP study may further clarify whether osimertinib plus chemotherapy improves outcomes for patients with high-risk co-mutations. - The DOI for the study is 10.20892/j.issn.2095-3941.2025.0566. - The study was supported by a grant from AstraZeneca China.