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Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung
Yoshiko Urata1, Nobuyuki Katakami2, Satoshi Morita2
1Yoshiko Urata, Miyako Satouchi, and Shunichi Negoro, Hyogo Cancer Center, Akashi; Nobuyuki Katakami and Reiko Kaji, Institute of Biomedical Research and Innovation; Daichi Fujimoto, Kobe City Medical Center General Hospital, Kobe; Satoshi Morita, Kyoto University Graduate School of Medicine, Kyoto; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Takashi Seto, National Kyushu Cancer Center; Yoichi Nakanishi, Kyushu University, Graduate School of Medical Sciences, Fukuoka; Yasuo Iwamoto and Masashi Kanehara, Hiroshima City Hospital, Hiroshima; Norihiko Ikeda, Tokyo Medical University, Tokyo; Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka; Haruko Daga, Osaka City General Hospital; Fumio Imamura, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka; Isao Goto, Osaka Medical College, Takatsuki; Hideo Saka, National Hospital Organization Nagoya Medical Center; Tetsuya Oguri, Nagoya City University Graduate School of Medical Sciences, Nagoya; Shunichi Sugawara, Sendai Kousei Hospital, Sendai; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Kazuhiko Nakagawa, Kinki University Faculty of Medicine, Osaka-Sayama, Japan. urata@hp.pref.hyogo.jp.
Purpose:
The epidermal growth factor receptor (EGFR) tyrosine kinase has been an important target for non-small-cell lung cancer. Several EGFR tyrosine kinase inhibitors (TKIs) are currently approved, and both gefitinib and erlotinib are the most well-known first-generation EGFR-TKIs. This randomized phase III study was conducted to investigate the difference between these two EGFR-TKIs.
Patients And Methods:
Previously treated patients with lung adenocarcinoma were randomly assigned to receive gefitinib or erlotinib. This study aimed to investigate the noninferiority of gefitinib compared with erlotinib. The primary end point was progression-free survival (PFS).
Results:
Five hundred sixty-one patients were randomly assigned, including 401 patients (71.7%) with EGFR mutation. All baseline factors (except performance status) were balanced between the arms. Median PFS and overall survival times for gefitinib and erlotinib were 6.5 and 7.5 months (hazard ratio [HR], 1.125; 95% CI, 0.940 to 1.347; P = .257) and 22.8 and 24.5 months (HR, 1.038; 95% CI, 0.833 to 1.294; P = .768), respectively. The response rates for gefitinib and erlotinib were 45.9% and 44.1%, respectively. Median PFS times in EGFR mutation-positive patients receiving gefitinib versus erlotinib were 8.3 and 10.0 months, respectively (HR, 1.093; 95% CI, 0.879 to 1.358; P = .424). The primary grade 3 or 4 toxicities were rash (2.2% for gefitinib v 18.1% for erlotinib) and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation (6.1%/13.0% for gefitinib v 2.2%/3.3% for erlotinib).
Conclusion:
The study did not demonstrate noninferiority of gefitinib compared with erlotinib in terms of PFS in patients with lung adenocarcinoma according to the predefined criteria.
Insights
This study found gefitinib was not noninferior to erlotinib for non-small-cell lung cancer progression-free survival. Toxicity profiles differed, with erlotinib showing more rash and gefitinib more liver enzyme elevations.
Area of Science:
- Oncology
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are crucial for non-small-cell lung cancer (NSCLC) treatment.
- Gefitinib and erlotinib are established first-generation EGFR-TKIs used in clinical practice.
Purpose of the Study:
- To compare the efficacy and safety of gefitinib versus erlotinib in previously treated patients with lung adenocarcinoma.
- To determine if gefitinib is noninferior to erlotinib based on progression-free survival (PFS).
Main Methods:
- A randomized phase III clinical trial involving 561 patients with lung adenocarcinoma.
- Patients were assigned to receive either gefitinib or erlotinib.
- Progression-free survival (PFS) was the primary endpoint, with overall survival and response rates as secondary endpoints.
Main Results:
- The study did not meet its primary endpoint, failing to demonstrate noninferiority of gefitinib compared to erlotinib for PFS (median PFS: 6.5 vs. 7.5 months).
- Overall survival was similar between the two groups (median OS: 22.8 vs. 24.5 months).
- Significant differences in toxicity were observed: higher rates of rash with erlotinib and elevated liver enzymes (ALT/AST) with gefitinib.
Conclusions:
- Gefitinib did not show noninferiority to erlotinib in terms of PFS for lung adenocarcinoma patients.
- The distinct toxicity profiles suggest different safety considerations for each drug.
- Further research may explore optimal sequencing or combination strategies for EGFR-TKIs.
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