| Background and Purpose:The current regimens for patients with advanced lung squamous cell carcinoma(LSQCC)who experience progression with first-line chemotherapy are still deficient.Apatinib,an oral small molecular receptor tyrosine kinase inhibitor(TKI),exerts antiangiogenic and antineoplastic function through selectively binding and inhibiting vascular endothelial growth factor receptor-2(VEGFR-2).S-1,an oral anti-metabolite,is an effective regimen for patients with advanced LSQCC.This study was conducted to explore the efficacy and safety of apatinib plus S-1 as second-line or above-line treatment for advanced LSQCC(a phase II,single-arm,multicentre,prospective study).Patients and Methods:We enrolled 48 patients onto this study from December 2016 to January 2019.Patients who experienced treatment failure with at least first-line treatments by platinum-based chemotherapy were screened for eligibility.Eligible patients had measurable disease(per RECIST version 1.1)and an Eastern Cooperative Oncology Group(ECOG)performance status 0-1 or 2.Patients were treated with oral apatinib(250mg once daily)and S-1(capsules 40–60 mg twice daily,days 1–14),every 3weeks for a cycle,until disease progression or intolerance to adverse events(AE).Progression-free survival(PFS)was set as the primary endpoint.Overall response rate(ORR),disease control rate(DCR),overall survival(OS),and the safety profile were considered to be the secondary endpoints.Results:During follow-up to April 2019,23 patients demonstrated a partial response(PR),17 patients achieved stable disease(SD)and 8 patients had progressive disease(PD).The ORR and the DCR were 47.9%(23/48)and 83.3%(40/48)for the entire lesions.The ORR was 55.6%(20/36)for second-line group and was 25.0%(3/12)for third-line or above group(?~2=3.667,P=0.067).The DCR was 94.4%(34/36)for second-line group and was 50.0%(6/12)for third-line or above group(?~2=8.900,P=0.002).The m PFS and m OS were 4.5(range,1.6-11.0;95%CI 3.681-5.319)and 14.0(range,3.0-26.0;95%CI12.780-15.220)months for the whole group.Patients who received second-line treatment had more favorable m PFS than did third-line or above treatment(4.6 months;95%CI3.494–5.706 months vs.3.5 months,95%CI 2.093-4.907 months;P=0.025).Moreover,the second-line treatment subgroup definitely enhanced m OS than the third-line or above treatment subgroup(14.0 months;95%CI 12.334-15.666 months vs.9.0 months;95%CI3.788-14.212 months,P=0.000).According to the multivariate Cox analysis,different treatment-lines were the independent factors of PFS(P=0.003)and OS(P=0.000).Toxicities were tolerable or could be clinically managed.The most common grade 1 to 2adverse events(AE)were anemia(n=24,50.0%)、fatigue(n=20,41.6%)、thrombocytopenia(n=19,39.6%)、hand-foot syndrome(n=15,31.2%)and hypertension(n=15,31.2%).In addition,serious adverse events(SAE)were thrombocytopenia(n=3,6.3%),hand-foot skin syndrome(n=2,4.2%),and hemoptysis(n=1,2.1%).Conclusions:Apatinib combined with oral S-1 as second-line or above-line treatment in advanced LSQCC patients is a potentially effective regimen with an acceptable safety profile,and is a valid treatment option.However,further prospective,phase III,randomized controlled studies are still warranted to explore the efficacy. |
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