Osimertinib Plus Chemotherapy Approved in the EU, Japan as First-line Treatment for Patients with EGFR-mutated Advanced NSCLC
Results from the FLAURA-2 trial, which were presented at the IASLC’s 2023 World Conference on Lung Cancer, have led to two more approvals of osimertinib with the addition of pemetrexed and platinum-based chemotherapy as first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC).
The Japanese Pharmaceuticals and Medical Device Agency and the European Commission approved the combination on June 25 and July 5, respectively. The combination was previously approved by the US Food and Drug Administration (FDA) on February 16.
The FLAURA-2 results showed osimertinib plus chemotherapy extended median progression-free survival (PFS) by nearly 9 months compared to standard of care in patients with EGFR-positive NSCLC whose tumors have exon 19 deletions or exon 21 (L858R) mutations.
In the trial, osimertinib with the addition of chemotherapy reduced the risk of disease progression or death by 38% by investigator assessment compared to osimertinib monotherapy, which is the first-line global standard of care (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). Median PFS was 25.5 months for patients treated with osimertinib plus chemotherapy, an 8.8-month improvement versus osimertinib monotherapy (16.7 months). PFS results from blinded independent central review (BICR) were consistent with the results by investigator assessment, showing 29.4 months median PFS with osimertinib plus chemotherapy, a 9.5-month improvement compared to osimertinib monotherapy (19.9 months) (HR 0.62; 95% CI 0.48-0.80; nominal p=0.0002).
Results from a prespecified exploratory analysis of FLAURA-2 patients with brain metastases at baseline showed osimertinib plus chemotherapy reduced the risk of central nervous system (CNS) disease progression or death by 42% compared to osimertinib monotherapy (HR 0.58; 95% CI 0.33-1.01). With 2 years of follow up, 74% of patients treated with osimertinib plus chemotherapy had not experienced CNS disease progression or death versus 54% of patients treated with osimertinib monotherapy.
While the overall survival (OS) results remained immature at the second interim analysis (41% maturity), a trend towards an OS benefit was observed with osimertinib plus chemotherapy versus osimertinib alone (HR 0.75; 95% CI 0.57-0.97). Those data were presented at the 2024 European Lung Cancer Congress. The trial continues to assess OS as a key secondary endpoint.
Health Canada Authorizes Amivantamab in Combination with Carboplatin and Pemetrexed
On July 3, Health Canada, through a Priority Review, approved amivantamab in combination with carboplatin and pemetrexed for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. The FDA previously approved the combination on March 1.
Both approvals were based on results from the phase III PAPILLON study, which showed amivantamab in combination with carboplatin and pemetrexed significantly improved PFS, reducing the risk of disease progression or death by 60% versus carboplatin and pemetrexed alone in patients with previously untreated NSCLC with EGFR exon 20 insertion mutations. The primary results were presented at the 2023 European Society for Medical Oncology Congress.
The PAPILLON study compared treatment with amivantamab in combination with platinum-based chemotherapy to treatment with platinum-based chemotherapy alone in patients with treatment-naïve, locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Among 151 patients who received amivantamab in combination with platinum-based chemotherapy, the median duration of treatment was 9.7 months (range: 0.1 to 26.9 months), with 76% were exposed for 6 months or longer and 38% were exposed for more than one year.
