Zorifertinib improves progression-free survival (PFS) when compared to gefitinib or erlotinib as first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastases, according to research presented at the ASCO Annual Meeting 2023.
Both systemic and intracranial PFS benefits were seen with zorifertinib, and no new safety signals were identified, according to study presenter Yi-Long Wu, MD, of Guangdong Lung Cancer Institute in China.
This phase 3 trial (ClinicalTrials.gov Identifier: NCT03653546) enrolled 439 patients who had EGFR-mutant NSCLC with CNS metastases. The patients had received no prior systemic therapy and no brain radiotherapy.
The patients were randomly assigned to receive zorifertinib (n=220) or to a control group that received gefitinib or erlotinib (n=219). Zorifertinib was given at 200 mg twice daily. Gefitinib was given at 250 mg daily, and erlotinib was given at 150 mg daily. Baseline characteristics were similar between the arms.
The primary endpoint was PFS. At a median follow-up of 20.4 months, the median PFS was 9.6 months in the zorifertinib arm and 6.9 months in the control arm (hazard ratio [HR], 0.719; 95% CI, 0.580-0.893; P =.0024).
Intracranial PFS was 15.2 months in the zorifertinib arm and 8.3 months in the control arm (HR, 0.467; 95% CI, 0.352-0.619; P <.0001).
The objective response rate (ORR) was 68.6% in the zorifertinib arm and 58.4% in the control arm (odds ratio [OR], 1.533; 95% CI, 1.051-2.293). The median duration of response was 8.2 months and 6.8 months, respectively (HR, 0.801; 95% CI, 0.613-1.047; P =.0997).
The intracranial ORR was 75.0% in the zorifertinib arm and 64.2% in the control arm (OR, 1.658; 95% CI, 0.993-2.768). The median duration of intracranial response was 12.4 months and 7.0 months, respectively (HR, 0.521; 95% CI, 0.352-0.773; P =.0009).
Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 65.9% of patients in the zorifertinib arm and 18.3% of those in the control arm. The most common grade 3 or higher TRAEs in the zorifertinib arm were rash (13.6%), acneiform dermatitis (13.6%), and diarrhea (13.2%).
TRAEs leading to permanent discontinuation of study treatment occurred in 5.9% of patients in the zorifertinib arm and 2.3% of those in the control arm. TRAEs leading to dose modifications occurred in 70.5% and 17.4%, respectively.
There was 1 death in the zorifertinib arm that may have been related to the treatment, but researchers were unable to determine the cause of death.
This trial was the first randomized, controlled, open-label, multinational study designed specifically to address an unmet medical need for patients with EGFR-mutant NSCLC and CNS metastases, Dr Wu said. The results suggest that zorifertinib “provides a novel, well-validated, first-line option” for this population, he added.
Disclosures: This research was sponsored by Alpha Biopharma (Jiangsu) Co, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Wu Y-L, Zhou Q, Wang J, et al. Randomized phase 3 study of first-line AZD3759 (zorifertinib) versus gefitinib or erlotinib in EGFR-mutant (EGFRm+) non–small-cell lung cancer (NSCLC) with central nervous system (CNS) metastasis. ASCO 2023. June 2-6, 2023. Abstract 9001.
