|The following article features coverage from the European Society for Medical Oncology 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Apatinib, a VEGFR2 inhibitor, combined with gefitinib prolonged progression-free survival (PFS) compared with gefitinib alone among patients with previously untreated, EGFR-mutated non-small cell lung cancer (NSCLC), according to results from a phase 3 trial presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
“Apatinib combined with gefitinib is expected to become a new first-line treatment option for EGFR-mutant NSCLC,” said Li Zhang, MD, of the Sun Yat-sen University Cancer Center in China, who was the presenter of the study.
The phase 3 ACTIVE trial (ClinicalTrials.gov Identifier: NCT02824458) randomly assigned 313 patients with exon 19 deletion (ex19del) or L858R EGFR mutations to receive apatinib plus gefitinib or placebo plus gefitinib. The primary endpoint was PFS assessed by blinded independent radiology review and secondary endpoints included investigator-assessed PFS, overall survival (OS), objective response rate (ORR), duration of response (DOR), and safety.
The median age at baseline was 59 years and 41% of patients were male. Approximately three-quarters of patients were nonsmokers and most had stage IV disease. EGFR exon 19 deletion (ex19del) were present in 52% of patients.
The ORR was similar between arms, at 77.1% and 73.7% with apatinib plus gefitinib compared with gefitinib, respectively (P =.5572). The DOR, however, was longer in the apatinib plus gefitinib group at 12.9 months compared with 9.3 months in the gefitinib arm.
The addition of apatinib to gefitinib prolonged PFS with a median of 13.7 months compared with 10.2 months with gefitinib (hazard ratio [HR], 0.71; 95% CI, 0.54-0.95; P =.0189). When stratified by mutation, patients with the ex19del mutation had improved PFS (HR, 0.67; 95% CI, 0.45-0.99) versus patients with the L858R mutation (HR, 0.72; 95% CI, 0.48-1.09).
Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred more frequently in the apatinib arm, affecting 84.1% of patients compared with 37.7% of patients in the gefitinib arm. TEAEs led to dose interruption in 59.9% and 22.7% of patients in the apatinib plus gefitinib and gefitinib arms, respectively. Discontinuation occurred in 5.1% of patients in the apatinib plus gefitinib arm compared with 3.2% in the gefitinib arm. Grade 3 or higher TEAEs that occurred more frequently in the apatinib plus gefitinib group included hypertension and proteinuria.
Dr Zhang concluded that “apatinib plus gefitinib were generally well tolerated with manageable toxicities.” He added that, “This dual oral regimen will provide more convenient treatment for patients who required long-term administration.”
Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.
Zhang L, Zhao H, Zhang Z, et al. ACTIVE: Apatinib plus gefitinib versus placebo plus gefitinib as first-line treatment for advanced epidermal growth factor receptor-mutant (EGFRm) non-small-cell lung cancer (NSCLC): A multicentered, randomized,double-blind, placebo-controlled phase III trial (CTONG1706). Presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract LBA50.