Adjuvant apatinib following concurrent chemoradiotherapy in high-risk nasopharyngeal carcinoma: A multicenter, prospective, phase 2 study.

Abstract

e18019 Background: Nasopharyngeal carcinoma (NPC) patients with T4 or N2–3 or lymph node >3cm diseases have a high risk of metastasis. This study aimed to evaluate the efficacy and safety of adjuvant apatinib in high-risk NPC. Methods: This open-label randomized clinical trial was conducted at five hospitals in China. NPC patients with newly histologically confirmed non-keratinizing (according to WHO histologically type), tumor staged as T4 or N2-3 or lymph node>3cm, M0 (according to the 8th AJCC edition), an Eastern Cooperative Oncology Group performance status of 0 or 1, and sufficient organ function were included. All patients were randomly assigned (1:1) to receive apatinib mesylate tablet for adjuvant treatment (the dose was 250 mg, orally, qd, 28 days for an observation period, six cycles) of high-risk metastasis NPC after Intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy(cisplatin) or only observation after IMRT with concurrent chemotherapy (CCRT). The primary endpoint was 3-year progression-free survival (PFS). Secondary endpoints included 3-year overall survival (OS), 3-year distant metastasis-free survival (DMFS), 3-year local recurrence-free survival (LRFS), and toxicity. Results: From March 2018 to September 2020, 86 patients were randomized to the CCRT group(n=44) or the CCRT plus apatinib group(n=42). The median follow-up time was 56 months (IQR 40.0-58.6). 3-year PFS was 78.6% (95% CI 66.3-90.9; 12 disease progressions and 7 deaths) in the CCRT plus apatinib group and 54.5% (95% CI 39.8-69.2; 23 disease progressions and 16 deaths) in the CCRT group (log-rank P = 0.027). Compared with the CCRT group, the 3-year OS was higher in the CCRT plus apatinib group (88.1% [95% CI 81.7-99.3] vs 75.0% [95% CI 62.2-87.7]). The 3-year DMFS was significantly longer in the CCRT plus apatinib group (85.4% [95% CI 75.1-96.3]) than the CCRT group (59.1% [95% CI 44.6-73.6]). 3-year LRFS was similar in the two groups (log-rank P = 0.743). Grade 3 or 4 adverse events were reported in 26.2% of patients in the CCRT plus apatinib group and 6.8% in the CCRT group. The treatment-related AEs of grades 3-4 with hypertension (n=6, 14.3%), hand-foot syndrome (n=4, 9.5%), elevated aminotransferase (n=3, 7.1%), headache (n=3, 7.1%), and leukopenia (n=3,7.1%) in the CCRT plus apatinib group. Conclusions: This phase II trial showed that adjuvant apatinib following concurrent chemoradiotherapy significantly improved survival and was well tolerated in patients with high-risk NPC. Clinical trial information: NCT03612219 . CCRT group(n=44) CCRT+Apatinib group(n=42) P value 3-year PFS (95 CI%) 54.5% (39.8-69.2) 78.6%(66.3-90.9) 0.027 3-year OS (95 CI%) 75.0% (62.2-87.7) 88.1%(81.7-99.3) 0.029 3-year DMFS (95 CI%) 59.1% (44.6-73.6) 85.4%(75.1-96.3) 0.009 3-year LRFS (95 CI%) 92.9% (85.1-100.0) 95.1%(88.7-100.0) 0.743 Grade 3-4 AEs, n (%) 3 (6.8%) 11(26.2%)