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

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.

Novel Nanocrystal Injection of Insoluble Drug Anlotinib and Its Antitumor Effects on Hepatocellular Carcinoma

“…Low solubility and poor oral bioavailability are common problems of some molecularly targeted drugs currently on the market (66). Taking gefitinib or sorafenib as examples, their poor oral absorptions mean large doses (250 mg/person/day for gefitinib and 800 mg/person/day for sorafenib) must be given to achieve therapeutic effects (67)(68)(69). Extreme poor water solubility makes intravenous preparations difficult to produce, and advanced intervention and perfusion treatment methods cannot be used.…”