Icotinib improves PFS and ORR in Chinese NSCLC patients with brain metastases
Icotinib improves progression-free survival (PFS) and objective response rate (ORR) vs whole-brain irradiation (WBI) plus chemotherapy in Chinese patients with non-small-cell lung cancer (NSCLC) and brain metastases, according to a phase III study presented recently at the 17th World Conference on Lung Cancer (WCLC).
Among 176 NSCLC patients who had at least three brain lesions, the primary endpoint of intracranial PFS more than doubled in the icotinib group (n=85) vs the WBI/chemotherapy group (n=91) (median, 10.0 vs 4.8 months; hazard ratio [HR], 0.56; p=0.014). [WCLC 2016, abstract PR03.03]
“Median PFS was 6.8 months in the icotinib group vs 3.4 months in the WBI/chemotherapy group [HR, 0.44; p<0.001],” reported investigator Professor Yi-Long Wu of the Guangdong Lung Cancer Institute, Guangdong General Hospital in Guangzhou, China.
“Intracranial ORR was 67.1 percent with icotinib vs 40.9 percent with WBR/chemotherapy, while overall ORR was 55.0 vs 11.1 percent [both p<0.001],” he continued. “The disease control rate [DCR] was 78.8 vs 54.8 percent [p=0.001], while intracranial DCR rate was 84.7 vs 67.3 percent [p=0.014].”
Patients (mean age, 58 years; 32 percent male) in the study were recruited from 17 sites across China. About 16 percent had symptomatic brain metastases, and 70.9 percent were nonsmokers. Almost 53 percent of patients had tumours harbouring EGFR exon 19 mutations, while 42.4 percent had EGFR exon 21 (L858R) mutations and 4.7 percent had uncommon diverse EGFR mutations.
The patients were randomized to receive either the small-molecule EGFR tyrosine kinase inhibitor (TKI) icotinib (125 mg orally, 3 times a day), or WBI (30 Gy/3 Gy or 10 fractions) plus concurrent or sequential chemotherapy for 4–6 cycles.
“Icotinib was well tolerated in the study, with only seven patients [8.2 percent] experiencing grade ≥3 adverse events vs 28 patients [26.2 percent] in the WBI/chemotherapy group,” said Wu. “The most common adverse events associated with icotinib treatment were increased liver transaminase and rash, while patients in the WBI/chemotherapy group most commonly experienced haematologic toxicity.”
“Although WBI is a standard of care for patients with brain metastases, the median survival is 4–6 months only. The combination of WBI with small-molecule EGFR inhibitors remains controversial, and there were no data from prospective randomized trials examining the efficacy of EGFR TIKs on brain metastases,” he said.
“Icotinib is currently indicated as second- or third-line therapy for patients with EGFR-mutant, advanced or metastatic NSCLC who failed at least one prior chemotherapy regimen. Our results indicate that icotinib should be used in first-line treatment of patients with advanced, EGFR-mutant NSCLC with brain metastases,” he suggested.