Abstract CT083: Apatinib for advanced bone and soft tissue sarcomas in stage IV: Focus on efficacy and safety
Authors: Liao Zhichao , Li Feng , Yang Yun , Yang Jilong 
Published: August 2018

Objective: Sarcomas are a group of malignant tumors originating from mesenchymal tissue with a variety of cell subtypes. Despite several major treatment breakthroughs, standard treatment using surgery, radiation, and chemotherapy has failed to improve overall survival. Therefore, there is an urgent need to explore new strategies and innovative therapies to further improve the survival rates of patients with sarcomas in stage IV. Apatinib is a new type of small molecule tyrosine kinase inhibitor that selectively targets VEGFR-2 and has shown encouraging anticancer activity in a wide range of malignancies. This single-arm, multi-center phase II study (NCT03120846) to assess efficacy and safety of Apatinib for sarcoma patients in Stage IV who failed to conventional therapies.

Methods: All sarcoma patients in stage IV failed to chemotherapy had at least one measurable extracranial tumor according to Response Evaluation Criteria In Solid Tumors 1.1 criteria (RECIST1.1). Apatinib was administered 500mg/daily on day 1 through 28 in each 4-week cycle. The primary endpoints were progression free survival (PFS), progression free survival rate (PFR), objective response rate (ORR) and disease control rate (DCR) at week 12. Treatment-related adverse effects (AEs) were reviewed and evaluated.

Results: From September 2015, 60 patients were recruited, including 33 males and 27 females (average age 43.7ys). Pathological types included osteosarcoma (n=9), undifferentiated polymorphic sarcoma (n=8), peripheral neuroectodermal tumor/Ewing's Sarcoma (n=7), malignant peripheral nerve sheath tumor (n=6), synovial sarcoma (n=5), leiomyosarcoma (n=5), fibrosarcoma (n=5), rhabdomyosarcom (n=5) and other sarcomas (n=10). Up to the Jun. 2018, 60 patients were assessable for side effects and 48 patients were assessable for efficacy. The median PFS was 8.72 months and the PFR at 12W was 79%. The median PFS of bone sarcoma patients was 7.87 months and the median PFS of soft tissue sarcoma patients was 8.93 months. At 12W, 5 patients achieved PR, 28 patients achieved SD, and 5 patients occurred disease progression. The ORR and DCR rate at 12W were 13.16% (5/38) and 86.84(33/38), respectively. 2 patients (3.33%, 2/60) had dose adjustment during treatment because of the uncontrolled grade III hypertension, reducing to 250 mg daily. One of them still could not control the hypertension and quitted the trial. Common AEs included hypertension (n=24), hand-foot-skin reaction (n=21), proteinuria (n=18), Anorexia (n=13), Fatigue (n=9), Pain (n=7), Diarrhea (n=6) and others. No grade 4 AEs occurred and 14 patients (23.33%) suffered from grade 3 AEs, mainly Hypertension, Hand-foot syndrome, and Proteinuria.

Conclusion: The ORR and DCR rate of Apatinib at 12W are 13.16% and 86.84%, respectively. The median PFS is 8.72 months and the PFR at 12W is 79%. Compared with Pazopanib (ORR=6%, 14/246; DCR=72.4%, 178/246) and anlotinib (ORR=11.45%, 19/166; DCR=73.49, 122/169; PFS-12W=57.23%), Apatinib is effective to many pathological types of sarcomas. Meanwhile, Apatinib is well tolerated, while hypertension, hand-foot-skin reaction, and proteinuria need to be noticed. This result supports future random controlled trial to further define Apatinib activity in stage IV sarcomas.

Citation Format: Zhichao Liao, Feng Li, Yun Yang, Jilong Yang. Apatinib for advanced bone and soft tissue sarcomas in stage IV: Focus on efficacy and safety [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT083.