What Is the Role of EGFR TKIs in Stage III NSCLC?

Previous research showed that gefitinib can improve DFS in certain NSCLC patients, raising the possibility that EGFR-targeted TKIs could be beneficial in the neoadjuvant setting.

Neoadjuvant and adjuvant treatment with erlotinib resulted in significantly improved progression-free survival compared with gemcitabine plus cisplatin in patients with stage IIIA-N2, EGFR-mutated non–small-cell lung cancer (NSCLC), according to a randomized trial.

“Cisplatin-based doublet chemotherapy as neoadjuvant treatment for stage IIIA-N2 NSCLC only gives patients [a] 5% 5-year overall survival benefit,” said Yi-Long Wu, MD, of Guangdong Lung Cancer Institute in China. Previous research showed that gefitinib can improve disease-free survival over chemotherapy in certain NSCLC patients, raising the possibility that EGFR-targeted tyrosine kinase inhibitors (TKIs) could be beneficial in the neoadjuvant setting.

Wu presented results of the CTONG 1103 trial at the European Society for Medical Oncology (ESMO) 2018 Congress, held in Munich. The trial randomized 72 patients with stage IIIA-N2 NSCLC and EGFR mutations to receive either neoadjuvant erlotinib for 42 days followed by surgery and 12 subsequent months of erlotinib, or 2 cycles of neoadjuvant chemotherapy with gemcitabine plus cisplatin (GC) followed by surgery and then 2 more cycles of the same regimen.

The objective response rate for neoadjuvant treatment was 54.1% with erlotinib and 34.3% with the GC regimen, for an odds ratio for response of 2.26 (95% CI, 0.87–5.84; P = .092). Following neoadjuvant therapy, 83.8% of erlotinib patients and 68.6% of GC patients underwent surgery; lymph node downstaging occurred in 13% of the erlotinib patients and in 4.2% of the GC patients.

The median progression-free survival with erlotinib was 21.5 months, compared with 11.9 months with GC, for a hazard ratio of 0.42 (95% CI, 0.23–0.76; P = .0003). The overall survival data were not yet mature at the time of the study’s presentation. There were no grade 3/4 adverse events in the erlotinib group, compared with 29.4% of the GC group. The authors noted that no unexpected adverse events were found.

“This is the first study to demonstrate progression-free survival superiority for erlotinib over gemcitabine plus cisplatin chemotherapy in the neoadjuvant/adjuvant setting of stage IIIA-N2 EGFR-mutated NSCLC,” Wu said, according to a press release.

Tony S. K. Mok, MD, of the Chinese University of Hong Kong, commented on the study for ESMO. “While the difference between EGFR TKI and chemotherapy is significant, the impact of neoadjuvant EGFR TKI is relatively disappointing,” he said, noting that the response rate was lower than what would be expected in stage IV disease, and only 13% of patients achieved a major pathologic response. “The reason for this is unclear, but one may have to query if duration of neoadjuvant EGFR TKI for 42 days is sufficient. Overall, this important study offers us the rationale to consider neoadjuvant EGFR TKI.”