Open-label, multi-center, phase II study of adjuvant pemetrexed plus cisplatin for completely resected stage IB to IIIA adenocarcinoma of the lung: APICAL trial

一项开放标签、多中心、II期临床研究,评估培美曲塞联合顺铂辅助治疗完全切除的IB期至IIIA期肺腺癌的疗效:APICAL试验

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Abstract

BACKGROUND: We aimed to evaluate the efficacy of postoperative adjuvant pemetrexed plus cisplatin (Pem-Cis) in pathologic stage IB-IIIA lung adenocarcinoma (LUAD) patients. METHODS: A prospective, phase II study was performed in seven institutions in South Korea. Patients with completely resected stage IB-IIIA LUAD received pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)). Adjuvant treatments were administered every 3 weeks for 4 cycles. The primary endpoint was to prove the Pem-Cis's superiority in terms of 2-year disease-free survival rate (DFSR) compared with historical control without adjuvant chemotherapy (50%). RESULTS: Between August 2015 and February 2018, 105 patients were enrolled in this study. Approximately 31.4% (n=33), 43.8% (n=46), and 24.8% (n=26) of patients had pathologic stage IB, II, and IIIA, respectively. Most of the patients underwent lobectomy (n=98, 93.3%). Moreover, 41.1% and 12.1% of the patients had epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase rearrangement. Four cycles of Pem-Cis were administered in 99 patients (94.3%). At a median follow-up of 57.7 months, the 2-year DFSR was 78.1%. Multivariable analysis showed that pathologic stage IIIA and EGFR mutation were significant risk factors for DFS. Grade 3 adverse events occurred in 10 patients (9.5%), and leukopenia (n=3, 2.9%) was the most common adverse event. CONCLUSIONS: Adjuvant Pem-Cis is superior to historical control without adjuvant treatment in terms of 2-year DFSR; the proportion of patients with stage IB and driver mutations were higher than that of patients in previous trials. Pem-Cis showed favorable tolerability as adjuvant chemotherapy (clinicaltrial.gov; Identifier: NCT02498860).

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