Adjuvant treatment with intercalated gefitinib (Iressa) plus platinum-based chemotherapy improved disease-free survival (DFS) compared with platinum-based chemotherapy alone in patients with completely resected stage II to IIIB EGFR-mutant non–small cell lung cancer (NSCLC), according to data from a phase 3 trial presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).¹
In the overall efficacy-evaluable population, the median DFS was 58.8 months (95% CI, 41.9-not reached [NR]) with intercalated gefitinib plus chemotherapy vs 41.9 months (95% CI, 21.9-NR) with chemotherapy alone (P = .0359). The benefit was more pronounced in patients with an EGFR exon 19 deletion and in those with stage III disease at baseline, whereas no DFS difference emerged in patients with an L858R mutation or stage II disease. Safety was reported as manageable in both arms, although EGFR-related toxicities occurred more frequently with the addition of gefitinib.
Key Takeaways
- Intercalated gefitinib plus adjuvant chemotherapy improved DFS vs chemotherapy alone in completely resected stage II–IIIB EGFR-mutant NSCLC (median DFS, 58.8 vs 41.9 months; P = .0359).
- The benefit was concentrated in patients with an exon 19 deletion and stage III disease; no benefit was seen with an L858R mutation or stage II disease.
- EGFR-related toxicities, including dermatitis acneiform and gastrointestinal and hepatic adverse effects, were more frequent with intercalated gefitinib, though overall safety was described as manageable.
How was the trial designed?
This multicenter, phase 3 trial, conducted in South Korea, randomly assigned patients with completely resected stage II to IIIB EGFR-mutated NSCLC (exon 19 deletion or L858R) in a 1:1 ratio to adjuvant intercalated gefitinib plus platinum-based chemotherapy or platinum-based chemotherapy alone. The primary end point was investigator-assessed DFS; safety and overall survival (OS) were secondary end points.
Baseline characteristics were generally balanced between arms. Median age was 62 years in both the intercalation and chemotherapy-alone arms. Female patients predominated in both arms (67.6% vs 70.3%, respectively), as did those with an ECOG performance status of 0 (54.9% vs 58.2%). Exon 19 deletion was more common than L858R in both arms (60.8% vs 39.2% in the intercalation arm; 58.2% vs 41.8% in the chemotherapy-alone arm), and stage III disease was more frequent than stage II disease in both arms (53.9% vs 46.1%, and 54.9% vs 45.1%, respectively).
What did the efficacy analysis show across subgroups?
With median follow-up of 41.8 months the DFS benefit with intercalated gefitinib plus chemotherapy was not uniform across biomarker- and stage-defined subgroups. Among patients with an exon 19 deletion, the median DFS was not reached (95% CI, 41.9 months-NR) with intercalation vs 21.2 months (95% CI, 14.4-NR) with chemotherapy alone (P = .0096). Among patients with an L858R mutation, the median DFS was 42.0 months (95% CI, 28.4-NR) vs 42.7 months (95% CI, 24.2-NR), respectively (P = .9036), showing no separation between arms.
A similar pattern held by disease stage. In patients with stage II disease, the median DFS was NR in either arm (95% CI, 41.9-NR; P = .4547). In patients with stage III disease, the median DFS was 42.0 months (95% CI, 25.0-NR) with intercalation vs 21.2 months (95% CI, 13.6-42.7) with chemotherapy alone (P = .0211).
What did the safety analysis show, and what are the next steps?
Safety was described as manageable in both treatment arms. EGFR-related toxicities including dermatitis acneiform as well as gastrointestinal and hepatic adverse effects occurred more frequently in the intercalation arm than with chemotherapy alone.
The investigators noted that these findings arrive as adjuvant osimertinib (Tagrisso) has become a recommended option for patients with completely resected stage IB to IIIA EGFR-mutant NSCLC harboring an exon 19 deletion or L858R mutation, administered with or without chemotherapy. Longer follow-up and further analyses of minimal residual disease dynamics were identified as warranted to help clarify the role of TKI- and/or chemotherapy-based adjuvant strategies in this population.
Reference
- Ahn BC, Lee JB, Lee Y, et al. A phase III randomized multicenter trial of adjuvant gefitinib plus chemotherapy versus chemotherapy in EGFR-mutant NSCLC. Presented at: International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, South Korea. Abstract OA04.01.
