Osimertinib administered in addition to chemotherapy showed more progression-free survival (PFS) benefit than just osimertinib in patients with epidermal growth factor receptor–mutated (EGFRm) advanced non–small cell lung cancer (NSCLC).
Osimertinib with the addition of chemotherapy showed a statistically significant and clinically meaningful progression-free survival (PFS) benefit compared with only osimertinib in patients with epidermal growth factor receptor–mutated (EGFRm) advanced non–small cell lung cancer (NSCLC) in the FLAURA2 study, according to results presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.
Data from studies that merged first-generation EGFR–tyrosine kinase inhibitors (EGFR-TKIs) with chemotherapy implied a synergistic effect, so researchers hypothesized that the combination of osimertinib with chemotherapy may give even greater PFS benefits than just osimertinib.1
The FLAURA2 study was a global, phase 3, open-label, randomized study evaluating the safety and efficacy of osimertinib in conjunction with platinum-pemetrexed chemotherapy vs osimertinib alone as first-line treatment for EGFRm advanced NSCLC. Osimertinib, an effective third-generation EGFR-TKI with central nervous system (CNS) activity, has garnered attention for its targeted inhibition of EGFR sensitizing and resistance mutations.
Total study participants were 557 patients who were randomly assigned 1:1 into 2 treatment arms consisting of osimertinib plus chemotherapy or osimertinib monotherapy. The combination arm included a regimen of osimertinib (80 mg daily) in addition to pemetrexed and cisplatin or carboplatin.
Patients who were eligible were 18 years or older (20 years or older in Japan), with pathologically confirmed nonsquamous locally advanced/metastatic NSCLC. Stable CNS metastases not needing steroids for at least 2 weeks were permitted. The primary end point was PFS by investigator evaluation per RECIST v1.1.
The HR shown was 0.62 (95% CI, 0.49-0.79; P < .0001) for PFS in the combination arm, indicating an 8.8-month growth in median PFS. Additionally, the objective response rate per investigator was markedly higher in the combination arm at 83% compared with the monotherapy arm of 76%. Safety analyses showed that the combination therapy was well-tolerated in general, with adverse events that proved controllable.
“Results from the study demonstrated a remarkable improvement in progression-free survival (PFS) with the osimertinib plus chemotherapy approach, showcasing a statistically significant reduction in disease progression risk compared to osimertinib monotherapy,” Pasi A. Jänne, MD, PhD, of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts, who led the FLAURA2 study, said in a statement.2
Researchers stated that further ongoing analyses consisted of CNS blinded independent central review (BICR) response and progression, patient-reported outcomes, postprogression end points, and circulating tumor DNA (ctDNA) analyses (resistance mechanisms and ctDNA dynamics).3
1. Jänne P, Planchard D, Cheng Y, et al. Osimertinib with/without platinum-based chemotherapy as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA2). Abstract presented at: 2023 World Conference on Lung Cancer; September 9-12, 2023; Singapore.
2. FLAURA2 results demonstrate osimertinib plus chemotherapy superior compared to osimertinib alone. News release. EurekAlert!; September 10, 2023. Accessed September 12, 2023. https://www.eurekalert.org/news-releases/1000706
3. Jänne P, Planchard D, Cheng Y, et al. Osimertinib with / without platinum-based chemotherapy as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA2). PowerPoint presented at: 2023 World Conference on Lung Cancer; September 9-12, 2023; Singapore.