Apatinib in combination with pemetrexed-platinum chemotherapy for chemo-naive non-squamous non-small cell lung cancer: a phase II clinical study
Mené sur 20 patients atteints d'un cancer du poumon non épidermoïde non à petites cellules de stade avancé n'ayant jamais reçu de chimiothérapie, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité de l'apatinib en combinaison avec une chimiothérapie à base de pémétrexed et sels de platine
Résumé en anglais
Objectives : Apatinib showed efficacy in non-small cell lung cancer (NSCLC). We conducted a 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 intravenously pemetrexed (500 mg/m 2) plus platinum-based chemotherapy (carboplatin AUC = 5 or cisplatin 75 mg/m 2) every 21 days for 6 treatment cycles, 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 toxicity.
Results : Twenty advanced and chemo-naive non-squamous NSCLC patients were enrolled and evaluated. The ORR and DCR were 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%, 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 in those with CNS metastasis at baseline was 3.8 (95%CI: 0.9-6.7) months ( 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 previous TKI targeted agents.
