FDA Approves Osimertinib in Stage III NSCLC

Osimertinib (Tagrisso; AstraZeneca) received its second new indication of the year, with yesterday’s FDA approval of the irreversible third-generation tyrosine kinase inhibitor (TKI) for use among adult patients who have unresectable stage III non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.^1,2

Data first presented at the American Society of Clinical Oncology meeting in June from the ongoing phase 3 LAURA trial (NCT03521154)³ were used for the FDA’s priority review of AstraZeneca’s application for the new indication.⁴

To receive osimertinib under this newest indication, which was based on positive primary end point data analysis for progression-free survival (PFS)—via RECIST 1.1 criteria—a patient’s disease must not have progressed during or after concurrent or sequential platinum-based chemoradiation. The TKI previously received a breakthrough designation as well, meaning the medication fulfilled an unmet treatment need for patients with serious and life-threatening conditions.⁵

“This approval represents a major breakthrough for patients with stage III, EGFR-mutated lung cancer who will now have the opportunity to benefit from osimertinib,” said Suresh Ramalingam, MD, executive director of Winship Cancer Institute of Emory University, Atlanta, US, and LAURA principal investigator, in a statement from AstraZeneca.⁴ “Patients treated with osimertinib lived without disease progression by more than 3 years in the LAURA trial, and this impressive benefit underscores the importance of diagnosing and testing lung cancer patients as early as possible.”

This newest approval follows the February 2024 FDA approval of osimertinib with chemotherapy for use also in adult patients but those not yet treated for locally advanced or metastatic EGFR-mutated NSCLC, based on results from the ongoing phase 3 FLAURA2 trial (NCT04035486), in which patients were randomized to treatment with osimertinib (n = 143) or placebo (n = 73). Those data showed a 38% reduced risk of death or disease progression (HR, 0.62; 95% CI, 0.49-0.79; P < .0001) with osimertinib/chemo compared with osimertinib alone and a 8.8-month better improved progression-free survival, at 25.5 vs 16,7 months.³

Hailed as a practice-changing drug even before yesterday’s approval, the LAURA trial data used to support the new indication show the significant benefits associated with osimertinib³:

• 84% reduced risk of disease progression or death (HR, 0.16; 95% CI, 0.10-0.24; P < .001) compared with placebo
• 39.1-month median PFS compared with 5.6-month PFS with placebo
• 74% PFS from osimertinib at 12 months compared with 22% seen with placebo
• 65% PFS from osimertinib at 24 months compared with 13% seen with placebo

Within the randomized, double-blind, placebo-controlled, multicenter LAURA trial, patients from 145 centers in 15 countries—the US, Europe, South America and Asia—received oral osimertinib at 80 mg each day until disease progression or unacceptable toxicity, or they met other discontinuation criteria. Patients also were allowed to cross over from the placebo arm to the treatment arm if they experienced disease progression.

The secondary end points for the LAURA trial are overall survival (OS), central nervous system PFS, and safety, and these investigations are ongoing. So far at 20% maturity, these data demonstrate the following benefits of osimertinib vs placebo⁶:

• Median OS of 54 months (95% CI, 46.5–not calculable [NC]) vs not reached (95% CI, 42.1-NC)
• Objective response rate of 57% (95% CI, 49%-66%) vs 33% (95% CI, 22%-45%)
• Disease control rate of 89% (95% CI, 83%-94%) vs 79% (95% CI, 68%-88%)

At this time, osimertinib is also being investigated in the phase 3 NeoADAURA trial and the phase 3 ADAURA2 trial for neoadjuvant and adjuvant uses, respectively.⁴

References

1. FDA approves osimertinib for locally advanced, unresectable (stage III) non-small cell lung cancer following chemoradiation therapy. News release. FDA. September 25, 2024. Accessed September 26, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-locally-advanced-unresectable-stage-iii-non-small-cell-lung-cancer#:~:text=On%20September%2025%2C%202024%2C%20the,concurrent%20or%20sequential%20platinum%2Dbased

2. Tagrisso (osimertinib) approved in the US for patients with unresectable, stage III EGFR-mutated lung cancer. News release. BusinessWire. September 26, 2024. Accessed September 26, 2024. https://www.businesswire.com/news/home/20240926874208/en/TAGRISSO%C2%AE-osimertinib-approved-in-the-US-for-patients-with-unresectable-Stage-III-EGFR-mutated-lung-cancer

3. Caffrey M. Osimertinib with chemo gains FDA approval for EGFR-mutated NSCLC. AJMC^®. February 19, 2024. Accessed September 26, 2024. https://www.ajmc.com/view/osimertinib-with-chemo-gains-fda-approval-for-egfr-mutated-nsclc

4. Tagrisso approved in the US for patients with unresectable, Stage III EGFR-mutated lung cancer. News release. AstraZeneca. September 26, 2024. September 26, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-us-approval-in-unresectable-lung-cancer.html

5. Expedited programs for serious conditions | drugs and biologics. FDA. May 2014. Accessed September 26, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics

6. Ramalingam SS, Kato T, Dong X, et al. Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: primary results of the phase 3 LAURA study. J Clin Oncol. 2024;42(suppl 17):LBA4. doi:10.1200/JCO.2024.42.17_suppl.LBA4