Osimertinib Enhances Progression-Free Survival in Stage III NSCLC

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Osimertinib (Tagrisso) showed statistically significant and highly clinically meaningful improvements in progression-free survival (PFS) when used for the treatment unresectable, stage III EGFR-mutated non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) vs placebo after CRT, according to findings from the phase 3 LAURA trial (NCT03521154).¹

This is the first EGFR inhibitor and targeted treatment to lead to benefits in PFS for the treatment of patients with stage III disease.

In the LAURA study, osimertinib’s safety and tolerability was consistent with what has been seen in prior trials and there were no new safety signals observed. Further, while data on overall survival (OS) showed a favorable trend for osimertinib, these findings were not mature at the time of this analysis and investigators will continue to evaluate OS as a secondary end point of the study.

“These results represent a major advance for patients with stage III EGFR-mutated lung cancer who have a high propensity for early progression and spread to the brain, and where no targeted therapy is available. LAURA shows osimertinib can provide impactful clinical benefit and could become the first targeted treatment option for patients with stage III disease,” said Suresh Ramalingam, MD, executive director of Winship Cancer Institute of Emory University, Atlanta, United States, and principal investigator in the trial, in a press release.

Findings from the trial will be presented at an upcoming medical meeting and shared with global regulatory authorities.

“These highly impactful results for the LAURA trial in this potentially curative early lung cancer setting further entrench [osimertinib] as the backbone therapy for EGFR-mutated lung cancer. These data together with the ADAURA [NCT02511106] data, reinforce the imperative to diagnose and treat patients with lung cancer as early as possible,” said Susan Galbraith, executive vice president, oncology research and development, AstraZeneca, in a press release.

About Osimertinib

Osimertinib is a third-generation, irreversible EGFR tyrosine kinase inhibitor (TKI) with proven clinical activity in NSCLC. The agent also works to combat central nervous system metastases. At a dose of 40mg and 80mg once daily orally, osimertinib has been used to treat patients across the globe and continues to be evaluated as a treatment option for patients across multiple stages of EGFR-mutated NSCLC.

On February 16, 2024, the FDA approved osimertinib plus chemotherapy for patients with advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. This approval was supported by findings from the phase 3 FLAURA2 trial (NCT04035486).

In addition to this indication, osimertinib is approved as an adjuvant therapy after tumor resection and as a frontline option in adult patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test, in combination with pemetrexed and platinum-based chemotherapy and for the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR TKI therapy.

About the LAURA Study

The randomized, double-blind, placebo-controlled, multicenter, international phase 3 LAURA study is evaluating osimertinib as maintenance therapy for the treatment of patients with locally advanced, unresectable NSCLC whose disease harbors an EGFR mutation and has not progressed after definitive platinum-based CRT.²

The study is investigating osimertinib at a dose of 80 mg, the initial dose, which will then be reduced to 40 mg given once daily vs placebo. Treatment will continue until disease progression, unacceptable toxicity, or other discontinuation criteria are met.

Adults aged 18 or older diagnosed with predominantly nonsquamous NSCLC in stage III, unresectable status are eligible for this study. Eligibility criteria include having 1 of the 2 common EGFR mutations associated with sensitivity to an EGFR TKI (EGFR exon 19 deletions or exon 21 L858R mutations), either alone or combined with other EGFR mutations, confirmed through specific tests. Patients must have undergone concurrent or sequential chemoradiation with at least 2 cycles of platinum-based chemotherapy and a radiation dose of 60 Gy ±10%, completed within 6 weeks prior to randomization without disease progression. Patients also must have a WHO performance status of 0 or 1 and a life expectancy of more than 12 weeks. Female patients not practicing abstinence must utilize contraception, not be breastfeeding, and test negative for pregnancy prior to starting the study drug or demonstrate non-childbearing potential.

The primary end point is PFS and secondary end points include OS, time to central nervous system PFS, objective response rate, duration of response, disease control rate, tumor shrinkage, time to death or distant metastases, time to treatment discontinuation, second PFS on a subsequent treatment, time to first subsequent therapy, patient-reported disease-related symptoms and health-related quality-of-life by EORTC QLQ-LC13 and EORTC QLQ-30 questionnaires, incidence of adverse events, and plasma concentrations of osimertinib and AZD5104.

REFERENCES:

1. TAGRISSO (osimertinib) demonstrated overwhelming efficacy benefit for patients with unresectable, stage III EGFR-mutated lung cancer in LAURA phase III trial. News release. AstraZeneca. February 19, 2024. Accessed February 19, 2024. http://tinyurl.com/sfbdkxxm

2. A global study to assess the effects of osimertinib following chemoradiation in patients with stage III unresectable non-small cell lung cancer (LAURA) (LAURA). ClinicalTrials.gov. February 1, 2024. Accessed February 19, 2024. https://clinicaltrials.gov/study/NCT03521154