Updated Trial Results Support Tagrisso as Standard-of-Care for EGFR-Mutated Lung Cancer

Image Credit: Adobe Stock Images/Sebastian Kaulitzki

Results from the Phase III LAURA and FLAURA2 trials and Phase II SAVANNAH and ORCHARD trials show that treatment with Tagrisso (osimertinib; AstraZeneca) produces significant survival benefits in patients with early-stage EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC), with potential efficacy in combination therapies for advanced disease.¹

These results, presented at the European Lung Cancer Congress (ELCC), solidified the role of Tagrisso as a foundational medication for this patient population.

“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,” said Myung-Ju Ahn, MD, PhD, professor, Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, in a press release “The continued overall survival (OS) 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.”

The global, randomized, double-blind, placebo-controlled Phase III LAURA trial enrolled 216 patients with unresectable, Stage III EGFRm NSCLC whose disease had not progressed following definitive platinum-based chemoradiotherapy. Patients were treated with 80 mg of once-daily Tagrisso or placebo until disease progression, unacceptable toxicity, or other discontinuation criteria were met.

Results showed a median OS of 58.8 months in the Tagrisso group compared to 54.1 months with placebo. Notably, 78% of patients in the placebo group switched to Tagrisso upon experiencing disease progression. AstraZeneca noted that the high crossover rate could dilute the observed survival difference, making it harder to detect a significant benefit of earlier Tagrisso use. The hazard ratio was 0.67 (95% CI, 0.40-1.14) with 31% maturity. The trial will continue assessing OS, and no new safety signals have been identified.

The ongoing global Phase II SAVANNAH trial enrolled 369 patients with EGFRm, locally advanced, or metastatic NSCLC with mesenchymal-epithelial transition overexpression and/or amplification whose disease progressed on first-line Tagrisso. Patients were randomly assigned to receive 300 mg or 600 mg once daily, or 300 mg twice daily of Orpathys (savolitinib) in combination with 80 mg of once-daily Tagrisso, or a combination of 300 mg twice daily Orpathys and placebo. The primary endpoint is overall response rate (ORR), with key secondary endpoints that included progression-free survival (PFS) and duration of response (DoR).

Early results showed that Tagrisso plus Orpathys achieved a 56% ORR, a median DoR of 7.1 months, and a median PFS of 7.4 months. The safety profile was consistent with previous studies, with grade 3 or higher adverse events (AEs) reported in 57% of patients.

The open-label, multi-center, Phase II ORCHARD trial evaluated 247 patients with advanced EGFRm NSCLC whose disease progressed on first-line Tagrisso. The study assessed 10 different Tagrisso-based combinations, with a primary endpoint of ORR and key secondary endpoints that included PFS and DoR.

Results from the Tagrisso plus Datroway (datopotamab deruxtecan) module showed an ORR of 43% in the 6 mg group and 36% in the 4 mg group. Median PFS was 11.7 months and 9.5 months, respectively. At nine months, 64% of patients in the 6 mg group remained responsive compared to 15% in the 4 mg group. Grade 3 or higher AEs occurred in 34% of patients on the 4 mg dose and 56% on the 6 mg dose. No new safety signals were identified.

The randomized, open-label, multi-center, global Phase III FLAURA2 trial evaluated 557 patients with locally advanced or metastatic EGFRm NSCLC. All patients received 80 mg of once-daily Tagrisso with chemotherapy (pemetrexed plus cisplatin or carboplatin) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks. The trial’s primary endpoint was PFS.

Results showed a median PFS of two years, regardless of the duration of pemetrexed maintenance therapy. The safety profile of the Tagrisso-chemotherapy combination was consistent with known profiles of both medicines. Grade 3 or higher chemotherapy-related AEs were reported in 16% of patients who received three to less than nine months of pemetrexed maintenance and 10% of patients who received over nine months. Chemotherapy discontinuation rates due to AEs were 18% for the three-to-nine-month group and 10% for the over nine-month group.¹

“Having now treated more than one million patients around the world, Tagrisso has repeatedly transformed expectations for patients with EGFR-mutated lung cancer by not only extending survival but also showing it is possible to maintain quality of life during cancer treatment,” said Susan Galbraith, EVP, oncology hematology R&D, AstraZeneca, in the press release. “The breadth of data at ELCC reinforce Tagrisso as the backbone therapy for patients with this disease and show that adding Orpathys or Datroway at the time of disease progression can help prolong patients’ responses to treatment.”

Reference

1. New study results reinforce Tagrisso as the backbone therapy for EGFR-mutated lung cancer across stages and settings. AstraZeneca. March 26, 2025. Accessed March 26, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/new-study-results-reinforce-tagrisso-as-the-backbone-therapy-for-egfr-mutated-lung-cancer-across-stages-and-settings.html