Chinese Study Shows Icotinib Noninferior to Gefitinib in Advanced NSCLC
In the noninferiority ICOGEN trial reported in Lancet Oncology, Yuankai Shi, MD, of the Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs. Beijing, and colleagues compared the oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor icotinib with gefitinib (Iressa) in Chinese patients with previously treated advanced non–small cell lung cancer (NSCLC). The study showed that icotinib, which is given three times daily, was noninferior to gefitinib in progression-free survival and might offer a better adverse event profile.
Study Details
In this phase III trial, 395 patients aged 18 to 75 years with NSCLC who had not responded to one or more platinum-based chemotherapy regimens were randomized to receive icotinib at 125 mg three times per day or gefitinib at 250 mg once daily until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival.
The icotinib and gefitinib groups were well matched for age (median, 57 years in both), sex (59% and 57% men), smoking status (51% and 52% nonsmokers), Eastern Cooperative Oncology Group performance status (0 or 1 in 87% and 89%), histology (adenocarcinoma in 75% and 77%), metastatic sites (eg, lymph nodes in 71% and 67%, bone in 41% and 39%), and disease stage (IV in 81% and 83%). More patients in the gefitinib group had mutant EGFR (59% vs 43%) and had received at least two prior chemotherapy regimens (45% vs 37%).
Progression-Free Survival Outcome
Median progression-free survival was 4.6 months in the icotinib group vs 3.4 months in the gefitinib group, with the hazard ratio (HR) of 0.84 (95% confidence interval [CI] = 0.67–1.05, P = .13) meeting the criterion for noninferiority. Subgroup analyses showed that hazard ratios consistently nonsignificantly favored icotinib.
Icotinib improved progression-free survival in the subgroup of patients without adenocarcinoma (HR = .61, P = .035), but this benefit did not differ significantly from that in patients with adenocarcinoma (HR = .88, P = .32; P = .27 for interaction). There was no difference in hazard ratios between EGFR mutant and EGFR wild-type subgroups (P = .41 for interaction).
Objective response rates were 27.6% in the icotinib group vs 27.2% in the gefitinib group, including rates of 62.1% and 52.8% in the EGFR mutant subgroups. Median overall survival was 13.3 months (95% CI = 11.1–16.2 months) in the icotinib group vs 13.9 months (95% CI = 11.4–17.3 months) in the gefitinib group. Overall, 28% of the icotinib group and 36% of the gefitinib group received subsequent therapies after progression.
Adverse Events
The most common adverse events of any grade occurring in at least 20% of either treatment group were rash (41% of icotinib group and 49% of gefitinib group) and diarrhea (22% and 29%). Grade 3 or 4 adverse events occurred in 7% vs 10% of patients; only diarrhea (2% of gefitinib patients) and pain (2% of patients in each group) occurred in more than 1% of either group.
The icotinib group had a lower frequency of drug-related adverse events of any grade (61% vs 70%, P = .046) and a lower frequency of drug-related diarrhea of any grade (19% vs 28%, P = .033). Four gefitinib patients were withdrawn for having more than 2 weeks of treatment interruption due to intolerable adverse events, whereas no patients in the icotinib had treatment interrupted due to adverse events. No cases of interstitial lung disease were reported, and no deaths were considered treatment-related in either group.
The investigators concluded: “The ICOGEN study established the noninferiority of icotinib when compared with gefitinib, showing that icotinib is a valid therapeutic option for patients with NSCLC as a second-line or third-line treatment, although patients might find taking icotinib three times a day an inconvenience. Furthermore, patients with EGFR mutations are more likely to benefit from icotinib than those without.”
Funding was provided by Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.
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®.
