ASCO24: Tagrisso reduces progression by 84% in unresectable EGFRm lung cancer

AstraZeneca’s Tagrisso (osimertinib) has demonstrated a significant reduction in the risk of tumor progression or death in patients with unresectable EGFR-mutated non-small-cell lung cancer (NSCLC) following chemoradiotherapy (CRT), according to the results of the Phase III LAURA study showcased at the American Society of Clinical Oncology (ASCO) annual meeting. This data positions the third-generation EGFR tyrosine kinase inhibitor as a potential new standard of care in this specific treatment setting.

David Spigel, an ASCO expert, noted that these findings could change clinical practice immediately once the drug's label is expanded, emphasizing that patients will be treated with Tagrisso where it’s accessible.

Immune checkpoint inhibitors like AstraZeneca’s Imfinzi (durvalumab) have been a standard treatment for unresectable NSCLC over recent years. However, while the PACIFIC study indicated no superior outcomes for EGFR-mutated patients, smaller studies have suggested potential benefits from targeting this mutation.

Tagrisso is already approved for first-line treatment of metastatic EGFR-mutant NSCLC and as an adjuvant therapy for resectable cases post-surgery. In the LAURA trial, 216 patients with Stage III EGFR-mutant NSCLC were randomized to receive daily oral Tagrisso or a placebo after completing platinum-based CRT. The primary endpoint was progression-free survival (PFS), with Tagrisso showing a median PFS of 39.1 months compared to 5.6 months for the placebo group. One-year PFS rates were 74% for Tagrisso versus 22% for placebo, increasing to 65% and 13% respectively at two years.

Principal investigator Suresh Ramalingam indicated that it is still early to determine if Tagrisso will extend overall survival (OS), the study’s secondary goal. Although OS results are not yet statistically significant, an interim analysis with 20% maturity hinted at a favorable trend for Tagrisso with a hazard ratio of 0.81. Importantly, over 80% of patients originally on placebo crossed over to Tagrisso after disease progression. Spigel commended the study designers for allowing this crossover, noting that while it complicates establishing an OS benefit, it was ethically correct.

The LAURA study, which is expected to be completed by mid-2026, will continue to evaluate OS. Additionally, Tagrisso significantly reduced the occurrence of new lesions both within and outside the chest, particularly in the brain. Only 6% of patients on Tagrisso developed new brain metastases compared to 29% on placebo. Overall, new lesions developed in 22% of Tagrisso-treated patients versus 68% in the placebo group.

No new safety concerns were identified in the LAURA trial. Expectedly, radiation pneumonitis was more frequent among those receiving Tagrisso at 48% compared to 38% with placebo, although most cases were mild. Severe cases (Grade ≥3) of radiation pneumonitis were rare, with only two instances in the Tagrisso group. Adverse event-related treatment discontinuations were higher with Tagrisso at 13% versus 5% for placebo.

Ramalingam highlighted that the extended treatment duration with Tagrisso—almost fourfold compared to placebo—likely contributed to the higher reporting of adverse events. This underscores the need for careful monitoring during prolonged treatment courses.

In conclusion, the LAURA trial results suggest that Tagrisso could become a new standard treatment for patients with unresectable EGFR-mutated NSCLC post-CRT, given its significant benefits in delaying tumor progression and reducing new lesion development, particularly in the brain. The study's ongoing efforts will further clarify its impact on overall survival.