In the Japanese phase III IMPACT trial reported in the Journal of Clinical Oncology, Tada et al found that adjuvant gefitinib did not improve disease-free survival vs cisplatin/vinorelbine in patients with completely resected stage II to IIIA EGFR-mutant non–small cell lung cancer (NSCLC).
In the multicenter open-label trial, 232 eligible patients were randomly assigned between September 2011 and December 2015 to receive gefitinib at 250 mg once daily for 24 months (n = 116) or cisplatin at 80 mg/m2 on day 1 plus vinorelbine at 25 mg/m2 on days 1 and 8 every 3 weeks for four cycles (n = 116). The primary endpoint was disease-free survival. Approximately 65% of patients had pathologic stage III disease; all 232 also had an EGFR mutation (exon 19 deletion or L858R).
Disease-Free Survival
At data cutoff in December 2020, median follow-up was 70 months. Median disease-free survival was 35.9 months (95% confidence interval [CI] = 30.0–47.7 months) in the gefitinib group vs 25.1 months (95% CI = 17.7–41.8) months in the cisplatin/vinorelbine group. However, Kaplan-Meier curves crossed at approximately 4 years after surgery, with no significant difference between groups being observed (hazard ratio [HR] = 0.92, 95% CI = 0.67–1.28, P = .63). Rates at 5 years were 31.8% vs 34.1%.
A total of 76 vs 71 patients received subsequent therapy after relapse. Among 66 vs 64 receiving drug therapy, 43 vs 59 received EGFR tyrosine kinase inhibitor treatment and 23 vs 4 received cytotoxic chemotherapy.
KEY POINTS
- Although gefitinib was associated with early improvement in disease-free survival, survival curves crossed at approximately 4 years after surgery.
- No difference in overall survival was observed.
Kaplan-Meier curves for overall survival exhibited no separation during follow-up, with no significant difference between groups being observed (HR = 1.03, 95% CI = 0.65–1.65, P = .89). Rates at 5 years were 78.0% vs 74.6%.
Adverse Events
Grade ≥ 4 adverse events occurred in 4% of patients in the gefitinib group (all grade 4) vs 62% of the cisplatin/vinorelbine group. Grade 4 events occurred in 59% of the cisplatin/vinorelbine group; all but one were hematologic adverse events, most commonly neutropenia.
The most common adverse events of any grade in the gefitinib group were increased alanine aminotransferase (69%) and aspartate aminotransferase levels (65%) and skin toxicity, including dermatitis acneiform in 58% and rash in 38%. Any-grade neutropenia, leukopenia, nausea, and anorexia occurred in more than 80% of the cisplatin/vinorelbine group. Three treatment-related deaths were observed in the cisplatin/vinorelbine group, due to cerebral hemorrhage, suicide, and pneumonia.
The investigators concluded, “Although adjuvant gefitinib appeared to prevent early relapse, it did not prolong disease-free survival or overall survival. However, similar disease-free survival and overall survival may justify adjuvant gefitinib in the selected patient subsets, especially those deemed ineligible for platinum-doublet adjuvant therapy; however, this was not a noninferiority trial.”
Tetsuya Mitsudomi, MD, PhD, of the Division of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
