Osimertinib After CRT Yields PFS Benefit in EGFR-Mutated NSCLC

“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," according to Suresh S. Ramalingam, MD, FACP, FASCO.

A statistically significant improvement in progression-free survival (PFS) was observed with osimertinib (Tagrisso) in patients with stage III EGFR-mutated non–small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) vs placebo and CRT, according to a press release on findings from the phase 3 LAURA trial (NCT03521154) from AstraZeneca.¹

The trial assessed 216 patients in the aforementioned population. While overall survival (OS) showed a favorable trend in the osimertinib arm, the data were not mature at the time of the analysis. Moving forward, investigators will continue to assess OS as a secondary end point.

Investigators noted no new safety concerns, and additional data will be presented at an upcoming meeting.

“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,” lead study author Suresh S. Ramalingam, MD, FACP, FASCO, executive director of Winship Cancer Institute of Emory University, said in the press release.

The double-blind, randomized, placebo-controlled study was created to assess the efficacy and safety of osimertinib after CRT. CRT could be given concurrently or sequentially, and if patients did not have progression after 6 weeks of completing CRT, they could receive osimertinib or placebo. If progression occurred, patients in the placebo arm could be unblinded and given osimertinib.

The primary end point was PFS, and secondary end points included OS, objective response rate, and duration of response.

Patients were given osimertinib at 80 mg daily, and the dose could be reduced to 40 mg. Matched placebo was given in the placebo plus CRT arm. Treatment was administered until disease progression, unacceptable toxicity, or discontinuation criteria were met.

Patients were enrolled if they had histologically documented NSCLC that was mostly nonsquamous, had an EGFR mutation, been given concurrent or sequential CRT with at least 2 cycles of platinum-based chemotherapy and total radiation of 60 Gy ± 10%. Exclusion criteria included having mixed small cell and NSCLC histology, a history of interstitial lung disease before CRT, and symptomatic pneumonitis after CRT.

Of note, osimertinib plus chemotherapy was recently approved by the FDA for patients with locally advanced or metastatic NSCLC harboring exon 19 deletions or exon 21 L858R mutations.² Supporting data came from the phase 3 FLAURA 2 trial (NCT04035486). In this trial, the median PFS was 25.5 months (95% CI, 24.7-not estimable) with osimertinib plus chemotherapy vs 16.7 months (95% CI, 14.1-21.3) with osimertinib only (HR, 0.62; 95% CI, 0.49-0.79; P <.0001).

The FDA previously granted priority review to a supplemental new drug application for the osimertinib combination as a treatment for the aforementioned population in October 2023.³

Additionally, osimertinib is being investigated in the phase 3 NeoADAURA trial (NCT04351555). Osimertinib will be assessed with and without chemotherapy for patients with EGFR-mutated resectable NSCLC. Results are expected to be released later this year.

“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 data, reinforce the imperative to diagnose and treat patients with lung cancer as early as possible,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca concluded.¹

References

1. Tagrisso 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 20, 2024. https://shorturl.at/gzEV1
2. FDA approves osimertinib with chemotherapy for EGFR-mutated non-small cell lung cancer. News release. FDA. February 16, 2024. Accessed February 20, 2024. https://bit.ly/49AeXjy
3. Tagrisso plus chemotherapy granted priority review in the US for patients with EGFR-mutated advanced lung cancer. News release. AstraZeneca. October 16, 2023. Accessed February 20, 2024. https://bit.ly/3ZUDUm9