What are the findings of the FLAURA (FLAURA) and FLAURA 2 research articles regarding Non-Small Cell Lung Cancer (NSCLC) treatment?

From the Guidelines

Osimertinib is the preferred treatment for EGFR-mutated non-small cell lung cancer (NSCLC), with the option of adding chemotherapy for patients who can tolerate the additional toxicity and desire more aggressive treatment. The FLAURA trial, as reported in the NCCN clinical practice guidelines in oncology 1, demonstrated that first-line osimertinib (80mg daily) significantly improved progression-free survival (18.9 vs 10.2 months) and overall survival (38.6 vs 31.8 months) compared to first-generation EGFR tyrosine kinase inhibitors (erlotinib or gefitinib) in patients with advanced EGFR-mutated (exon 19 deletion or L858R mutation) NSCLC. Osimertinib also showed better CNS efficacy and a more favorable toxicity profile.

The FLAURA 2 trial, as described in the ASCO living guideline, version 2024.1 1, evaluated osimertinib plus chemotherapy (carboplatin-pemetrexed for 4 cycles followed by pemetrexed maintenance) versus osimertinib alone, finding that the combination significantly improved progression-free survival (25.5 vs 16.7 months) with manageable toxicity. The combination approach did increase adverse events, particularly hematologic toxicities like neutropenia and anemia. Key points from the FLAURA 2 trial include:

• Progression-free survival was longer with osimertinib plus chemotherapy (hazard ratio [HR], 0.62 [95% CI, 0.49 to 0.79]; P < .0001)
• Median PFS was longer with osimertinib plus chemotherapy in patients with CNS metastases at baseline (24.9 months v 13.8 months) and in patients with L858R exon 21 mutations (24.7 months v 13.9 months)
• Toxicity was higher with osimertinib plus chemotherapy (grade ≥3 adverse events [AEs] 64% v 27%)

These landmark trials have reshaped treatment algorithms, with osimertinib monotherapy now standard first-line therapy for EGFR-mutated NSCLC, while the osimertinib-chemotherapy combination represents an emerging option for patients who can tolerate the additional toxicity and desire more aggressive treatment. Other treatment options, such as amivantamab-vmjw in combination with chemotherapy, may be considered for patients with advanced NSCLC and EGFR mutations whose disease has progressed on or after osimertinib monotherapy, as shown in the MARIPOSA-2 trial 1.

From the FDA Drug Label

The efficacy of TAGRISSO in combination with pemetrexed and platinum-based chemotherapy was demonstrated in a randomized, multicenter, open-label trial (FLAURA2 [NCT04035486]) in patients with EGFR exon 19 deletion or exon 21 L858R mutation-positive locally advanced or metastatic NSCLC, who had not received previous systemic treatment for advanced disease. FLAURA2 demonstrated a statistically significant improvement in PFS for patients randomized to TAGRISSO in combination with pemetrexed and platinum-based chemotherapy as compared to TAGRISSO monotherapy Table 18. Efficacy Results in FLAURA2 according to Investigator Assessment Efficacy ParameterTAGRISSO with pemetrexed and platinum-based chemotherapy (N=279)TAGRISSO (N=278) Progression-Free Survival (PFS)* PFS events (%) 120 (43) 166 (60) Progressive disease (%) 95 (34) 158 (57) Death† (%) 25 (9) 8 (2. 9) Median PFS in months (95% CI) 25.5 (24.7, NE) 16.7 (14.1,21.3) Hazard Ratio (95% CI)‡ 0.62 (0.49,0.79) p-value‡§ <0.0001

The FLAURA2 study showed that osimertinib in combination with pemetrexed and platinum-based chemotherapy significantly improved progression-free survival (PFS) compared to osimertinib monotherapy in patients with EGFR mutation-positive locally advanced or metastatic NSCLC. The median PFS was 25.5 months in the combination arm and 16.7 months in the monotherapy arm, with a hazard ratio of 0.62 2.

• Key findings:
  • PFS: statistically significant improvement in the combination arm
  • ORR: 77% in the combination arm and 69% in the monotherapy arm
  • DoR: median duration of response was 24.9 months in the combination arm and 17.9 months in the monotherapy arm
• CNS efficacy:
  • CNS ORR: 80% in the combination arm and 76% in the monotherapy arm
  • CNS DoR: median duration of response was not estimable in the combination arm and 17.9 months in the monotherapy arm

From the Research

FLAURA and FLAURA 2 Research Articles in Lung Cancer

• The FLAURA study, published in 2018 3, compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).
• The study found that osimertinib significantly improved progression-free survival (PFS) compared to standard EGFR-TKIs, with a median PFS of 18.9 months vs. 10.2 months.
• The objective response rate was similar in both groups, with 80% of patients responding to osimertinib and 76% responding to standard EGFR-TKIs.

Efficacy and Safety of Osimertinib

• A meta-analysis published in 2025 4 found that osimertinib improved the objective response rate (ORR) by 72% compared to erlotinib and gefitinib.
• The study also found that osimertinib demonstrated highly effective impacts in disease control among NSCLC patients, with a disease control rate (DCR) of 94%.
• Another study published in 2022 5 found that osimertinib confirmed effectiveness and safety in the real world, although thromboembolism was more frequent than previously reported.

FLAURA China Study

• The FLAURA China study, published in 2021 6, assessed first-line osimertinib in Chinese patients with EGFR-mutated advanced NSCLC.
• The study found that osimertinib extended median PFS by 8.0 months compared to comparator EGFR TKI, with a median PFS of 17.8 months vs. 9.8 months.
• The study also found that osimertinib resulted in a clinically meaningful PFS and OS benefit versus comparator EGFR TKI in Chinese patients with EGFR-mutated advanced NSCLC.

Osimertinib Resistance

• A study published in 2022 7 discussed the therapeutic strategies for EGFR-mutated NSCLC patients with osimertinib resistance.
• The study found that osimertinib resistance is complex and can be triggered by EGFR-dependent and EGFR-independent pathways.
• The study discussed potential therapeutic strategies for NSCLC patients with osimertinib resistance, including combination therapies and targeted therapies.