Apatinib Plus Radiation Therapy or Not in Chemotherapy-Refractory Recurrent or Metastatic Oral Squamous Cell Carcinoma: A Pilot Study

Abstract

For patients (pts) with recurrent/metastatic oral squamous cell carcinoma (OSCC), treatment options are still unmet medical need. Apatinib, a new tyrosine kinase inhibitor targeting VEGFR-2, shows antitumor activity and manageable toxicities in multiple malignancies. This study aimed to explore apatinib alone or in combination with radiotherapy (RT) as second-line or beyond therapy in OSCC. Chemotherapy-refractory OSCC pts were recruited in this open-label exploratory study. Subjects were initially given 500 mg qd apatinib until disease progression or unacceptable toxicity. Dose reduction to 250 mg was allowed. Palliative local RT (GTV: 50-60 Gy/25-30 f; CTV: 40-50 Gy, 5 f/w) was given to Stage IVB pts who could tolerate concurrent RT. Herein, we reported the preliminary results at the cut-off date of Jan 10, 2018. Ten pts were treated between Jun 2017 and Nov 2017. The median age was 70 yrs; 30.0% were male; ECOG PS 0-1/2 was 70.0/30.0%; 40.0% had ≥ 2 lines of chemotherapy. All pts were evaluated for radiographic response and safety analyses. One (10.0%) pt had complete response (CR), 5 (50.0%) had partial response (PR), 2 (20.0%) had stable disease and 2 (20.0%) had progressive disease. The ORR was 60.0% and DCR was 80.0%. Among the 5 pts who received apatinib combined with RT, 1 CR and 4 PR were achieved. Seven (70%) pts experienced treatment related adverse events (TRAEs). Most TRAEs were in grade 1/2 and could be well-controlled by symptomatic treatments. The grade 3/4 AEs were hypertension (4/10, 40%), fistula (1/10, 10%), hand-foot skin reaction (1/10, 10%) and heart failure (1/10, 10%). The cases experienced fistula and heart failure were combination therapy treated pts. Fortunately, the symptoms were alleviated by administration interruption and symptomatic therapy. No treatment-related death occurred. Apatinib alone or plus RT is efficacious in pretreated OSCC pts, with acceptable toxic effects. Pts might benefit more from the combination therapy, but with high risk of fistula that should be cautiously managed. This study gives rationale clinical evidence to conduct further larger confirmatory clinical trials.