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

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/m2) plus cisplatin (75 mg/m2). 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).

Keywords: Adjuvant chemotherapy; cisplatin; non-small-cell carcinoma; pemetrexed.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-183/coif). YCK reports a company funding from Shin Poong Pharm. Co., Ltd. for this study; grants from AstraZeneca and Boehringer Ingelheim; payments from AstraZeneca, MSD, Yuhan, Roche, Boehringer Ingelheim, Ono, BMS and Amgen. The other authors have no conflicts of interest to declare.

2022 Translational Lung Cancer Research. All rights reserved.

Figures

Figure 1

Patients enrollment. ITT, intention-to-treat.

Figure 2

Kaplan-Meier curves for DFS of the overall population (n=105) (A), and DFS according to pathologic stages (B) and EGFR mutation (C). DFS, disease-free survival; EGFR, epidermal growth factor receptor; NC, not calculated.

Figure 3

Variability of performance status during adjuvant pemetrexed plus cisplatin treatment. ECOG, Eastern Cooperative Oncology Group; EOT, end of treatment.