Real-World Analysis: Osimertinib Shows Superior Survival for Patients With Atypical EGFR-Mutated mNSCLC

Osimertinib (Tagrisso) can help patients with atypical EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) live longer and with better tolerability than first-line tyrosine kinase inhibitors (TKIs), according to a recent study published in Lung Cancer.

Adam Barsouk, MD, of Abramson Cancer Center and Perelman School of Medicine, and colleagues investigated osimertinib versus afatinib (Gilotrif) and erlotinib (Tarceva) outcomes in patients with atypical EGFR mutations who were treated from 2007 to 2023. The retrospective analysis evaluated progression-free survival (PFS) and overall survival (OS).

“There are limited data assessing the relative outcomes for patients with atypical EGFR mutations treated with osimertinib, afatinib, and erlotinib. These TKIs have not been compared in a head-to-head analysis of treatment outcomes for atypical EGFR mutations, leaving a key gap in the data needed to inform the management of this patient population,” the researchers said.

The analysis included 355 patients of which 90% had classical EGFR mutations that were detected on next-generation sequencing or PCR testing. Atypical EGFR mutations were seen in the remaining 10% of the population. They included the following: G719X (6%), Exon 20 (3%), L861Q (2%), S768I (1%), and C797S (0.3%). Compound mutations were discovered in 6 patients.

Furthermore, baseline demographics and disease characteristics were similar among patients with classical versus atypical EGFR mutations.

The researchers determined that osimertinib, a third-generation TKI, showed superior median PFS (22 months) compared with afatinib (12 months) or erlotinib (9 months).

In addition, median OS was also better in patients who received osimertinib compared with the other 2 TKIs. Patients who received osimertinib saw an OS of 32 months versus 21 months with afatinib or 17 months with erlotinib.

Patients were also able to tolerate osimertinib better than afatinib and erlotinib. Only 19% of patients had a dose reduction because of an adverse event (AE) with osimertinib versus 24% with afatinib or 23% with erlotinib. Discontinuation rates because of AEs were lower for osimertinib compared with afatinib or erlotinib (1% vs 2%, respectively).

“In a large real-world analysis, osimertinib demonstrated superior progression-free and overall survival and improved tolerability compared to afatinib or erlotinib for atypical EGFR-mutated mNSCLC,” the researchers concluded.

Reference

Real-world outcomes of atypical EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) treated with osimertinib (osi) vs. afatinib or erlotinib | Lung Cancer