Efficacy and Safety of First-Generation EGFR-TKIs Combined with Chemotherapy for Treatment-Naïve Advanced Non-Small-Cell Lung Cancer Patients Harboring Sensitive EGFR Mutations: A Single-Center, Open-Label, Single-Arm, Phase II Clinical Trial

Jinghui Lin, Meifang Li, Shijie Chen, Lihong Weng, Zhiyong He, Jinghui Lin, Meifang Li, Shijie Chen, Lihong Weng, Zhiyong He

Abstract

Purpose: This single-center, open-label, single-arm, phase II clinical trial aimed to examine the efficacy and safety of the first-generation EGFR-TKIs combined with chemotherapy among treatment-naïve advanced non-small-cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations.

Materials and methods: Patients with advanced EGFR-mutant NSCLC were given concurrent gefitinib (250 mg orally daily) and 3-week cycle of carboplatin plus pemetrexed for 4 to 6 cycles, followed by gefitinib maintenance until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. This trial was registered at ClinicalTrials.gov (NCT02886195).

Results: Of the 21 patients enrolled in this study, a 76.2% ORR and 100% DCR were observed and a higher ORR was seen in patients with EGFR 21L858R mutations than in those with 19del mutations (P = 0.012). The subjects had a median PFS of 15.0 months and a median OS of 26.0 months, and numerically longer PFS was seen in patients with EGFR 21L858R mutations than in those with 19del mutations (P = 0.281). There were 15 NSCLC patients without cerebral metastases at baseline, with 4 cases developing cerebral metastases during the treatment, and the 6-, 12- and 24-month cumulative incidence rates of the central nervous system metastasis were 6.67%, 13.3% and 26.7%, respectively. There were 17 subjects with progressive diseases tested for EGFR T790M mutations, and 11 cases were positive for T790M mutations. Grade 3 toxicity included neutropenia (9.5%), leukopenia (4.8%), liver dysfunction (9.5%) and diarrhea (4.8%), and no grade 4 adverse events or treatment-related death occurred.

Conclusion: The combination of first-generation EGFR-TKIs and chemotherapy achieves a satisfactory PFS, ORR and DCR and well-tolerated toxicity in advanced NSCLC patients with EGFR mutations, notably in patients with EGFR L858R mutations.

Keywords: EGFR-TKIs; chemotherapy; clinical efficacy; combination strategy; non-small-cell lung cancer; toxicity.

Conflict of interest statement

The authors declare no conflicts of interest.

© 2021 Lin et al.

Figures

Figure 1
Figure 1
Maximum tumor change from baseline by the best overall response, as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, each bar represents the maximum change in the sum of the diameters of the target lesions of an individual patient.
Figure 2
Figure 2
Kaplan-Meier estimates of survival. (A) Progression-free survival; (B) overall survival; (C) comparison of progression-free survival between advanced NSCLC patients harboring EGFR 19del and L858R mutations; (D) comparison of overall survival between advanced NSCLC patients harboring EGFR 19del and L858R mutations.

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