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Adjuvant Gefitinib vs Cisplatin/Vinorelbine for Completely Resected EGFR-Mutant Stage II to IIIA NSCLC


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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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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