Combining recombinant human endostatin with third-generation EGFR-TKIs in advanced EGFR-sensitive mutant non-small cell lung cancer

Abstract

Background: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line options in advanced or metastatic EGFR mutant non-small cell lung cancer (NSCLC). This study aimed to compare the efficacy and safety of third generation EGFR-TKIs combined with recombinant human endostatin (Endostar) versus EGFR-TKIs alone in previously untreated advanced epidermal growth factor receptor (EGFR) mutant NSCLC patients.

Methods: A total of 118 untreated advanced EGFR-sensitive-mutant NSCLC patients from a single center were retrospectively included in the study. Of the patients, 71 received third-generation EGFR-TKIs (the T group) and 47 received combination of Endostar and third-generation EGFR-TKIs therapy (the E + T group). Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR), and adverse events (AEs) were evaluated.

Results: Compared to the T group, the E + T group had a significantly higher ORR (91.5% vs. 77.5%; P=0.047), and improved PFS (20.2 vs. 17.6 months; P=0.002) and OS (41.5 vs. 33.8 months; P=0.04). However, there was no significant difference in the DCR between the two groups (97.9% vs. 97.2%; P>0.99). Multivariate analysis identified the Eastern Cooperative Oncology Group performance status (ECOG-PS) score, brain metastasis, EGFR co-mutation, and treatment regimen as independent prognostic factors. Subgroup analysis showed that the E + T group had greater clinical benefits for patients with ≥2 distant metastatic organs (P=0.01) and EGFR/TP53 co-mutations (P=0.01). The incidence of AEs of any level was higher in the E + T group than the T group (53.2% vs. 45.1%, P=0.39).

Conclusions: In this real-world study, the combination of recombinant human endostatin and third-generation EGFR-TKIs significantly improved the ORR, PFS, and OS in previously untreated advanced EGFR-mutant NSCLC patients and thus represents a promising treatment option that requires further prospective evaluation.

Keywords: Endostar; Non-small cell lung cancer (NSCLC); epidermal growth factor receptor mutation (EGFR mutation); epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).

Figure 1

Flowchart of the patient inclusion process. EGFR, epidermal growth factor receptor; EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor; NSCLC, non-small cell lung cancer.

Figure 2

Distribution of the TP53 mutation (A) and EGFR compound mutations (B) in EGFR-mutant NSCLC patients. EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer.

Figure 3

Kaplan-Meier curves for PFS (A) and OS (B) in patients with advanced EGFR-mutant NSCLC in different treatment groups. T group, EFGR-TKIs group; E + T group, Endostar + EGFR-TKIs group. CI, confidence interval; EGFR, epidermal growth factor receptor; EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor; HR, hazard ratio; mOS, median overall survival; mPFS, median progression-free survival; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival.

Figure 4

Subgroup analysis of the PFS of patients with advanced EGFR-mutant NSCLC in the T and E + T groups. T group, EGFR-TKIs group; E + T group, Endostar + EGFR-TKIs group. CI, confidence interval; HR, hazard ratio; ECOG-PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor; NSCLC, non-small cell lung cancer; PFS, progression-free survival.

Figure 5

Kaplan-Meier curves for PFS in patients with or without at least a single metastasis or the TP53 co-mutation. (A,B) Kaplan-Meier curves for PFS in patients with <2 organs with metastasis and ≥2 organs with metastasis in the E + T and T groups. (C,D) Kaplan-Meier curves for PFS comparing patients without the TP53 co-mutation and with the TP53 co-mutation in the E + T and T groups. T group, EGFR-TKIs group; E + T group, Endostar + EGFR-TKIs group. CI, confidence interval; EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor; HR, hazard ratio; mPFS, median progression-free survival; PFS, progression-free survival.