Dataset Information

Efficacy and Safety of First-Generation EGFR-TKIs Combined with Chemotherapy for Treatment-Naive 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.

SUBMITTER: Lin J

PROVIDER: S-EPMC8216733 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAfatinib has been shown as a suitable option for the treatment of epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC) in randomized controlled trials. However, patients treated in real-world clinical practice, including elderly patients, and those with brain metastases or poor Eastern Cooperative Oncology Group (ECOG) performance statuses, are often excluded from these studies.ObjectiveTo report the final results, with a particular focus on patients enrolled in China, from a prospective phase IIIb, "near real-world" study of afatinib in tyrosine kinase inhibitor (TKI)-naïve Asian patients with EGFRm+ NSCLC.Patients and methodsNCT01953913 was conducted at 34 centers across Asia. Entry criteria were broad to reflect real-world settings. Patients received afatinib 40 mg/day until tumor progression, lack of clinical benefit, or poor tolerability. Assessments included safety, time to symptomatic progression (TTSP), and progression-free survival (PFS).Results541 patients were treated, of whom 412 were enrolled in China. Dose reductions were implemented in 28.7% of patients overall, and 17.7% of patients from China. Safety findings were consistent with phase III studies of afatinib. Median TTSP in all patients was 14.0 months (95% CI 12.9-15.9), and median PFS was 12.1 months (95% CI 11.0-13.6). Median TTSP (13.8 months, 95% CI 12.7-16.1) and PFS (11.4 months, 95% CI 10.9-13.7) were similar in patients from China to the overall population. Among patients from China who had dose reductions, TTSP was numerically longer than in those who did not (16.4 vs. 13.8 months; P = 0.0703), while PFS was significantly longer (13.9 vs. 11.1 months; P = 0.0275). Among patients from China with brain metastases, TTSP was numerically shorter than in those without (11.0 vs. 14.4 months; P = 0.0869), whereas PFS was significantly shorter (9.2 vs. 12.9 months; P = 0.0075).ConclusionsSafety data for afatinib when used in a "near real-world" setting in patients with EGFRm+ NSCLC was consistent with the known safety profile of afatinib. Supporting efficacy data of afatinib were provided in all patients, and in those enrolled in China. Tolerability-guided afatinib dose reduction allowed patients to remain on treatment and continue to experience clinical benefit.Trial registration number and date of registrationNCT01953913 (1 October 2013).