What is the progression-free period for osimertinib (Tagrisso) in patients with EGFR-mutated advanced Non-Small Cell Lung Cancer (NSCLC)?

Progression-Free Period for Osimertinib in EGFR-Mutated Advanced NSCLC

The median progression-free survival (PFS) with osimertinib monotherapy in patients with EGFR-mutated advanced NSCLC is 18.9 months for first-line treatment, while osimertinib combined with chemotherapy extends this to 25.5 months. 1

First-Line Osimertinib Treatment Data

Osimertinib Monotherapy

• In the FLAURA phase III randomized trial, osimertinib demonstrated superior efficacy compared to earlier generation EGFR-TKIs (erlotinib or gefitinib):
  • Median PFS: 18.9 months vs. 10.2 months (HR 0.46, P<0.001) 1, 2
  • Median duration of response: 17.2 months vs. 8.5 months 1
  • Objective response rate: 80% (similar to standard EGFR-TKIs at 76%) 2
  • Lower incidence of CNS progression: 6% vs. 15% 1
  • Fewer grade 3 or higher adverse events: 34% vs. 45% 1, 2

Osimertinib Plus Chemotherapy

The FLAURA2 trial demonstrated that adding chemotherapy (pemetrexed plus platinum) to osimertinib further improves outcomes:

• Median PFS: 25.5 months vs. 16.7 months with osimertinib alone (HR 0.62, P<0.001) 1, 3
• Median duration of response: 24.0 months vs. 15.3 months 1, 3
• Higher rate of grade 3 adverse events, primarily due to chemotherapy-related toxicities 1, 3

Special Populations

• Patients with CNS metastases at baseline: Median PFS with osimertinib plus chemotherapy was 24.9 months vs. 13.8 months with osimertinib alone 1
• Patients with L858R exon 21 mutations: Median PFS with osimertinib plus chemotherapy was 24.7 months vs. 13.9 months with osimertinib alone 1

Overall Survival Data

• Median overall survival with osimertinib monotherapy: 38.6 months vs. 31.8 months with earlier generation EGFR-TKIs (HR 0.8, P=0.046) 1, 4
• 18-month survival rate: 83% with osimertinib vs. 71% with standard EGFR-TKIs 2

Progression After Osimertinib

For patients who progress on osimertinib first-line therapy, subsequent treatment options include:

• Amivantamab plus chemotherapy: Median PFS of 6.3 months vs. 4.2 months with chemotherapy alone (HR 0.48, P<0.001) 1
• Amivantamab plus lazertinib plus chemotherapy: Median PFS of 8.3 months 1

Uncommon EGFR Mutations

• Osimertinib shows activity in patients with uncommon EGFR mutations:
  • Overall response rate: 47.6% (higher in first-line setting at 63.6%) 5
  • Median duration of response: 7.9 months 5
  • Patients with G719X-compound mutations show better outcomes (median PFS 13.7 months) 5

Clinical Implications

• Osimertinib monotherapy remains a standard first-line option for EGFR-mutated advanced NSCLC
• The combination with chemotherapy offers improved PFS but with increased toxicity
• Treatment selection should consider:
  1. Presence of CNS metastases (favors osimertinib-based therapy)
  2. Specific EGFR mutation type (exon 19 deletion vs. L858R)
  3. Patient's ability to tolerate potential chemotherapy-related adverse events

Pitfalls and Caveats

• PFS benefits with combination therapy come with increased toxicity (grade ≥3 AEs: 64% with combination vs. 27% with monotherapy) 1
• Resistance to osimertinib eventually develops in most patients, commonly via EGFR T790M mutation 1
• PD-1/PD-L1 inhibitor monotherapy is less effective in EGFR-mutated NSCLC regardless of PD-L1 expression 1
• Regular monitoring for disease progression is essential, with median time to progression around 18.9 months for monotherapy and 25.5 months for combination therapy