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News
Combining osimertinib and gefitinib as first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC) achieved an 82.1% response rate and eliminated classic resistance mutations — but the regimen was tough to tolerate. A phase 1/2 study found that only 56% of patients met the feasibility threshold, with high rates of diarrhea, rash, and other side effects driving frequent dose modifications.
A phase 1/2 study led by Dana-Farber Cancer Institute tested the combination of osimertinib (Tagrisso) and gefitinib (Iressa) as first-line treatment in patients with EGFR-mutated stage IV NSCLC. The results, presented at the IASLC 2026 World Conference on Lung Cancer, showed an impressive 82.1% objective response rate and a notable finding: no classic second-site EGFR resistance mutations (like T790M or C797S) were detected at progression — a key goal of the dual-blockade strategy.
Despite the promising resistance profile, the combination's median progression-free survival of 18.4 months was comparable to historical data for osimertinib alone, raising questions about whether the added drug delivers a meaningful efficacy boost. Resistance that did emerge was driven largely by bypass pathway alterations (MET, KRAS, BRAF, PIK3CA) or remained unexplained.
By the Numbers:
Why it matters: Blocking EGFR resistance mutations is a compelling strategy, but this study highlights a real-world tension — a regimen that suppresses resistance may still fail to improve outcomes if tolerability limits its delivery. These findings will shape how oncologists weigh dual EGFR targeting against monotherapy in frontline NSCLC.
