Epidermal growth factor receptor (EGFR)–targeting tyrosine kinase inhibitors (TKIs) are the recommended initial therapy for metastatic EGFR-mutant non-small cell lung cancer (NSCLC), based on prolonged progression free survival (PFS) and improved quality of life compared to chemotherapy in several phase III trials. For patients with resected stage II and III NSCLC, cisplatin-based adjuvant chemotherapy is currently the standard of care, regardless of EGFR mutation status. However, results from retrospective studies and the phase II SELECT study indicate that patients with EGFR-mutant stage IB–IIIA resected NSCLC might benefit from adjuvant EGFR TKIs.
The multicenter, randomized, open-label phase III ADJUVANT study (N = 222) examined the safety and efficacy of 24 months adjuvant treatment with the EGFR TKI gefitinib in comparison to four cycles of adjuvant chemotherapy (vinorelbine plus cisplatin) in patients with resected, stage II-IIIA (N1-N2) EGFR-mutated NSCLC. At a median follow-up of 36.5 months, adjuvant gefitinib was associated with a more than 10-month improvement in disease-free survival (DFS) over chemotherapy (28.7 months vs 18.0 months; HR 0.6, P = .0054), and the DFS benefit was consistent across all patient subgroups. However, there was no significant difference in three-year DFS rates between the two treatment arms (34% vs 27%; HR 0.74, P = .37), and OS data are not yet mature.
The adverse event (AE) profile associated with adjuvant gefitinib was generally mild and consistent with the known toxicity profile in advanced disease. The most common grade 3 AEs in patients receiving gefitinib were elevated alanine aminotransferase and asparate aminotransferase (2% each), while the most common grade 3 AEs associated with chemotherapy were neutropenia (34%), leukopenia (16%), and vomiting (9%). Serious AEs occurred less frequently in patients treated with gefitinib compared to chemotherapy (7% vs 23%). Patient-reported quality of life improvement from baseline to week 33 was significantly higher in patients treated with gefitinib compared to chemotherapy (P = .012).
The investigators concluded that the superior DFS, reduced toxicity, and improved quality of life observed with adjuvant gefitinib compared to chemotherapy support its use as a treatment option for patients with stage II-IIIA EGFR-mutated NSCLC. The authors of an accompanying commentary highlighted that overall survival data from this study and the ongoing ALCHEMIST trial will be important to determine the role of EGFR TKIs in the adjuvant setting. They pointed out that although gefitinib significantly improved DFS compared to chemotherapy, these results do not appear to be durable. After a period of approximately three to four years, the DFS curves for the two arms converged, suggesting there may be no long-term survival benefit for adjuvant gefitinib as compared to chemotherapy. The results might indicate that adjuvant EGFR TKIs could effectively suppress tumor growth during treatment but are not more effective than chemotherapy to cure microscopic disease.