Adjuvant gefitinib extends DFS, not OS vs. chemotherapy in NSCLC subset
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Adjuvant gefitinib may be a reasonable alternative to standard-of-care chemotherapy for patients with EGFR-positive stage II or stage IIIA non-small cell lung cancer, according to study results published in Journal of Clinical Oncology.
The DFS benefit observed with gefitinib (Iressa, AstraZeneca), an EGFR tyrosine kinase inhibitor, did not result in a significant difference in OS compared with standard chemotherapy, researchers acknowledged. However, the median OS of 75.5 months with adjuvant gefitinib was one of the longest observed in this patient population compared with historical data, according to Yi-Long Wu, MD, director of Guangdong Lung Cancer Institute at Guangdong General Hospital in China.
“Adjuvant chemotherapy has been the standard treatment for patients with resected lung cancer for the past 20 years, but only a 5% survival benefit has been seen. Patients with lung cancer with an EGFR mutation are a special population who could be successfully treated with EGFR-targeted TKIs in advanced-stage disease. The goal of CTONG1104 was to compare adjuvant chemotherapy with adjuvant gefitinib,” Wu told Healio.
The phase 3 CTONG1104 trial enrolled 222 patients with resected EGFR-positive stage II or IIIA NSCLC across 27 institutions between September 2011 and April 2014. Researchers randomly assigned 111 patients (median age, 58 years; 58.6% women; 73.9% never-smokers) adjuvant gefitinib dosed at 250 mg daily for 2 years. The other 111 patients (median age, 60 years; 58.6% women; 76.6% never-smokers) received a standard chemotherapy regimen of 25 mg/m2 vinorelbine on days 1 and 8 plus 75 mg/m2 cisplatin on day 1 of four 3-week cycles.
DFS in the intention-to-treat population served as the primary endpoint. OS, DFS at 3 years and 5 years, and 5-year OS served as secondary endpoints.
Previously reported data from CTONG 1104 showed gefitinib was associated with significantly longer median DFS than chemotherapy (28.7 months vs. 18 months; HR = 0.6; 95% CI, 0.42-0.87) and significantly higher 3-year DFS rates (34% vs. 27%; P = .013).
In the current analysis, Wu and colleagues reported long-term OS and DFS rates.
Median follow-up was 80 months.
One-hundred patients (45%) in the intention-to-treat population died during the study, with 52 deaths reported in the gefitinib group and 48 deaths reported in the chemotherapy group.
According to study results, median OS in the intention-to-treat population was 75.5 months with gefitinib vs. 62.8 months with standard chemotherapy (HR = 0.92; 95% CI, 0.62-1.36), and 5-year OS rates were 53.2% vs. 51.2%.
About two-thirds of patients (68.4%) in the gefitinib group experienced disease progression and received subsequent therapy, compared with 73.6% of patients who received chemotherapy.
Subsequent therapy had a substantial influence on OS, according to the researchers. Median OS among those in the gefitinib group who received further therapy was 57.4 months (95% CI, 37.8 to not calculable) compared with 28.7 months (95% CI, 23.8-40.8) among those who did not. For the chemotherapy group, median OS was 51.9 months (95% CI, 40.5 to not calculable) with subsequent treatment and 15.6 months (95% CI, 10-24.2) without it.
Researchers reported no statistically significant differences between the gefitinib and chemotherapy groups in updated rates of 3-year DFS (39.6% vs. 32.5%) or 5-year DFS (22.6% vs. 23.2%).
However, adjuvant gefitinib appeared significantly superior to adjuvant chemotherapy in median DFS (30.8 months vs. 19.8 months) with an HR among the per-protocol population of 0.51 (95% CI, 0.36-0.72), which represents a 49% decrease in risk for disease recurrence, Wu said.
“Although this DFS advantage did not translate to a significant OS difference, EGFR-mutant lung cancer still maintained sensitivity to EGFR TKIs at retreatment, with a relative risk of 46.4% and a disease control rate of 82.1%, which may have contributed to prolonged OS,” Wu added. “Taken together, the standard of care for resected stage II to stage IIIA EGFR-mutant NSCLC may include adjuvant first-generation EGFR TKI treatment without prior adjuvant chemotherapy.”
For more information:
Yi-Long Wu, MD, can be reached at Guangdong Lung Cancer Institute, Yuexiu Qu, Guangzhou 510080, China; email: syylwu@live.cn.
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