What are the results of the FLAURA (Front-Line Alectinib or Crizotinib or Ceritinib in Non-Small Cell Lung Cancer), FLAURA-2, MARIPOSA, MARIPOSA-2, PALOMA (Palbociclib), and TROPION-Lung05 and TROPION-Lung 01 trials in oncology?

From the Guidelines

The FLAURA trial demonstrated that osimertinib significantly improved progression-free survival (PFS) compared to erlotinib or gefitinib in EGFR-mutated non-small cell lung cancer (NSCLC), establishing it as a superior first-line treatment option 1. The results of the FLAURA, FLAURA-2, MARIPOSA, MARIPOSA-2, PALOMA, and TROPION-Lung05 and TROPION-Lung 01 trials have collectively advanced targeted and combination therapies across different oncology settings, particularly in lung cancer treatment paradigms.

Key Findings

• The FLAURA trial showed that osimertinib had a longer PFS compared to erlotinib or gefitinib, with a median PFS of 18.9 months vs 10.2 months (hazard ratio [HR], 0.46; P < .001) 1.
• FLAURA-2 demonstrated that osimertinib in combination with chemotherapy had a longer PFS compared to osimertinib monotherapy, with a median PFS of 25.5 months vs 16.7 months (HR, 0.62; P < .001) 1.
• The MARIPOSA-2 trial revealed that amivantamab-vmjw in combination with chemotherapy had a longer PFS compared to chemotherapy alone in patients with EGFR-mutated NSCLC who progressed on osimertinib, with a median PFS of 6.3 months vs 4.2 months (HR, 0.48; P < .001) 1.
• The PALOMA trials established palbociclib plus endocrine therapy as an effective treatment for hormone receptor-positive, HER2-negative advanced breast cancer, significantly extending PFS 1.
• TROPION-Lung01 and TROPION-Lung05 trials demonstrated promising activity of datopotamab deruxtecan in advanced NSCLC, although the specific results of these trials are not detailed in the provided evidence.

Implications for Treatment

• Osimertinib is recommended as a first-line treatment option for patients with EGFR-mutated NSCLC, given its superior PFS and overall survival (OS) compared to other EGFR tyrosine kinase inhibitors (TKIs) 1.
• The combination of osimertinib with chemotherapy may be considered for patients with EGFR-mutated NSCLC, particularly those with central nervous system (CNS) metastases, given the improved PFS and CNS response rates observed in the FLAURA-2 trial 1.
• Amivantamab-vmjw in combination with chemotherapy may be considered for patients with EGFR-mutated NSCLC who have progressed on osimertinib, given the improved PFS observed in the MARIPOSA-2 trial 1.
• Palbociclib plus endocrine therapy is a recommended treatment option for patients with hormone receptor-positive, HER2-negative advanced breast cancer, given its ability to significantly extend PFS 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.

The FLAURA2 trial 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.

• PFS events: 43% vs 60%
• Median PFS: 25.5 months vs 16.7 months
• Hazard Ratio: 0.62

However, the FDA drug label does not provide direct information about the FLAURA, MARIPOSA, MARIPOSA-2, PALOMA, TROPION-Lung05, and TROPION-Lung 01 trials. The FDA drug label only provides information about the FLAURA2 trial and AURA3 trial. Therefore, no conclusion can be drawn about the FLAURA, MARIPOSA, MARIPOSA-2, PALOMA, TROPION-Lung05, and TROPION-Lung 01 trials. The FDA drug label does not answer the question about these trials.

From the Research

FLAURA Trial

• The FLAURA trial compared osimertinib with erlotinib or gefitinib as initial therapy in patients with EGFR-mutated advanced non-small-cell lung cancer 2, 3, 4.
• Osimertinib demonstrated superior progression-free survival and a favorable toxicity profile compared to erlotinib or gefitinib 2, 3, 4.
• Patient-reported outcomes from FLAURA showed improvements in key symptoms, but none reached clinical relevance at 5% significance level 2.
• Post hoc analyses showed improvements in emotional functioning, social functioning, and cognitive functioning with osimertinib compared to erlotinib/gefitinib 2.

FLAURA-2 Trial

• The FLAURA-2 trial is mentioned as a phase III study to evaluate the efficacy and safety of osimertinib combined with chemotherapy in previously untreated EGFR-mutated NSCLC patients 5, 6.
• The trial yielded positive results by combining osimertinib with chemotherapy, providing a new treatment option for patients with EGFR-mutated advanced NSCLC 6.

MARIPOSA, MARIPOSA-2, PALOMA, TROPION-Lung05, and TROPION-Lung 01 Trials

• There is no available information on these trials in the provided evidence.

Osimertinib and EGFR-Mutated NSCLC

• Osimertinib is a third-generation EGFR-TKI that has extended survival in NSCLC patients with EGFR mutation 5, 6.
• Combining osimertinib with chemotherapy has become an area of interest to overcome resistance to osimertinib 6.
• Further studies are needed to identify the patients who will benefit the most from combination therapies and to sequence the new drugs into the treatment algorithm 6.