Apatinib in combination with pemetrexed-platinum chemotherapy for chemo-naive non-squamous non-small cell lung cancer: a phase II clinical study

Abstract Objectives Apatinib showed efficacy in non-small cell lung cancer (NSCLC). We conducted this phase II clinical study to assess the efficacy and safety of apatinib in combination with pemetrexed-platinum chemotherapy in non-squamous NSCLC (Clinical Trial Registration: ChiCTR1800015920). Materials and methods Patients received oral apatinib (250 mg/d) with intravenous pemetrexed (500 mg/m2)-platinum (carboplatin AUC = 5 or cisplatin 75 mg/m2) chemotherapy every 21 days for 6 treatment cycles, and then maintained with apatinib 250 mg/d until progressive disease or intolerable toxicity. The primary endpoint was the objective response rate (ORR). The secondary endpoints included the progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and safety. Results Twenty advanced and chemo-naive non-squamous NSCLC patients were enrolled and evaluated. The ORR and DCR was 80% and 100%, respectively. The median PFS (mPFS) and median OS (mOS) for total patients was 7.7 (95%CI: 3.1-12.3) and 20.1 (95%CI: not available, NA) months. In the TKI-pretreated and treatment-naive subgroup, the ORR was 90% vs.70%, and the mPFS was 8.9 (95%CI: 5.5-12.3) vs.5.7 (95%CI: 0.1-11.3) months, respectively (P = 0.433). The mPFS in the responders without central nervous system (CNS) metastasis at baseline was 10.0 (95%CI: 6.1-13.9) months, and it was 3.8 (95%CI: 0.9-6.7) months in those with presence of CNS metastasis at baseline (P =  0.041, HR = 0.283, 95%CI: 0.084-0.948). Toxicities mainly included grade I-II hand-foot syndrome, hypertension, proteinuria and myelosuppression. Conclusion Apatinib in combination with pemetrexed-platinum chemotherapy showed good efficacy and tolerable toxicity in advanced non-squamous NSCLC, especially for those who failed to prior TKI targeted therapies.