Study results presented at the European Lung Cancer Congress (ELCC) 2025 demonstrate the role of osimertinib (Tagrisso; AstraZeneca), as monotherapy across stages and settings of EGFR-mutated non–small cell lung cancer (NSCLC).1
LAURA Trial Update
Updated results from the LAURA phase 3 trial showed an improved trend toward overall survival (OS) benefit with osimertinib compared with placebo in patients with unresectable, stage III EGFR-mutated NSCLC (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.40-1.14; maturity, 31%). Median OS was 58.8 months (95% CI, 54.1-not estimable [NE]) in patients treated with osimertinib compared with 54.1 months with placebo (95% CI, 42.1-NE), despite 78% of patients on placebo receiving subsequent treatment with osimertinib upon progression. The trial will continue to assess OS as a key secondary endpoint at the final analysis.
SAVANNAH Trial
Results from the SAVANNAH phase 2 trial showed osimertinib plus 300-mg, twice-daily savolitinib demonstrated a clinically meaningful and durable objective response rate (ORR) in patients with EGFR-mutated NSCLC with high levels of MET overexpression and/or amplification whose disease progressed on first-line treatment. Among patients screened for enrollment in SAVANNAH, an estimated 62% had tumors with MET overexpression and/or amplification, and approximately 34% met the defined high MET level cutoff.
Researchers reported confirmed an ORR of 56% (95% CI, 45%-67%), with a median duration of response (DOR) of 7.1 months (95% CI, 5.6-9.6). Median progression-free survival (PFS) was 7.4 months (95% CI, 5.5-7.6).
Safety results and discontinuation rates due to adverse events were consistent with the established profiles of each medicine and no new safety concerns were reported.
Savolitinib is an oral, MET tyrosine kinase inhibitor being jointly developed and commercialized by AstraZeneca and HUTCHMED.
ORCHARD Trial
First results from the osimertinib plus datopotamab deruxtecan-dlnk module of the ORCHARD phase 2 platform trial showed the combination demonstrated promising efficacy and manageable safety in patients with advanced EGFR-mutated NSCLC whose disease progressed on treatment with Tagrisso.
The module enrolled an all-comer population of patients with EGFR-mutated NSCLC and evaluated 2 doses of datopotamab deruxtecan-dlnk, 4 or 6 mg/kg, which, when used with osimertinib, demonstrated similar ORRs of 43% (80% CI, 31%-55%) and 36% (80% CI, 25%-49%), respectively. PFS and DOR results favored the 6-mg/kg dose with a median PFS of 11.7 months (95% CI, 8.3-NC) and 64% of patients continuing to respond at 9 months versus a median PFS of 9.5 months (95% CI, 7.2-9.8) and 15% of patients continuing to respond at 9 months on the 4-mg/kg dose.
Datopotamab deruxtecan-dlnk is a TROP2-directed antibody–drug conjugate discovered by Daiichi Sankyo and is being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
FLAURA2 Phase 3 Trial
An exploratory post-hoc analysis of the FLAURA2 phase 3 trial assessed PFS by length of exposure to pemetrexed maintenance treatment in patients with locally advanced (stage IIIB-IIIC) or metastatic (stage IV) EGFR-mutated NSCLC. Patients were treated with osimertinib with the addition of chemotherapy (pemetrexed plus cisplatin) followed by maintenance treatment with osimertinib and chemotherapy (pemetrexed) or osimertinib alone. Results showed a median PFS of >2 years regardless of length of pemetrexed maintenance exposure, with a trend associating longer PFS with longer pemetrexed treatment.
Previously presented OS data from the second interim analysis showed a favorable trend with the studied treatment plus chemotherapy arm (HR, 0.75; 95% CI, 0.57-0.97; maturity, 41%), with consistent results across all prespecified subgroups. The trial will continue to assess OS as a key secondary endpoint.
In a statement issued by the company, Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, noted: “A critical goal in treating every patient with lung cancer is to not only extend a patient’s life but also maintain quality of life while on treatment. The continued overall survival trend seen here at ELCC in the unresectable stage III setting and the promising data for combinations that can address progression in the advanced setting, together reinforce osimertinib as an effective, safe and convenient treatment for patients with EGFR-mutated lung cancer across stages and lines of treatment.”
Reference
- AstraZeneca. New study results reinforce TAGRISSO (osimertinib) as the backbone therapy for EGFR-mutated lung cancer across stages and settings. March 25, 2025. Accessed April 1, 2025. www.astrazeneca-us.com/media/press-releases/2025/New-study-results-reinforce-TAGRISSO-osimertinib-as-the-backbone-therapy-for-EGFR-mutated-lung-cancer-across-stages-and-settings.html