First-line concomitant EGFR-TKI + chemotherapy versus EGFR-TKI alone for advanced EGFR-mutated NSCLC: a meta-analysis of randomized phase III trials

ABSTRACT

Introduction

A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor – receptor (EGFR) mutation. Chemotherapy (ChT) given in combination with an EGFR-TKI in this setting is of interest.

Methods

We conducted a meta-analysis of phase III randomized trials comparing EGFR-TKI + ChT vs. EGFR-TKI alone as first-line therapy for advanced NSCLC harboring an activating EGFR mutation.

Results

Three studies evaluated gefitinib + ChT (NEJ009, GAP-Brain, and Noronha et al.) and another evaluated osimertinib + ChT (FLAURA-2). Those four eligible studies included 1413 patients with non-squamous NSCLCs, 826 (58%) with an exon-19 deletion (ex19del) and 541 (38%) with EGFR^L858R. The EGFR-TKI + ChT combination was significantly associated with prolonged PFS (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.45–0.59]; p < 0.0001) and OS (HR: 0.69 [0.52–0.93]; p = 0.01). PFS was particularly improved for patients with brain metastases (HR: 0.41[0.33–0.51]; p < 0.00001).

Conclusions

For patients with untreated, advanced, EGFR-mutated NSCLCs, the EGFR-TKI + ChT combination, compared to EGFR-TKI alone, was associated with significantly prolonged PFS and OS. However, further studies are needed to identify which patients will benefit the most from the combination.

Registration

PROSPERO CRD42024508055

KEYWORDS:

• Non-small cell lung cancer
• EGFR
• meta-analysis
• chemotherapy
• osimertinib
• gefitinib

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Author contributions

T. Landre and C. Chouaïd contributed to the study’s conception and design. Data acquisition, analyses, interpretation, and manuscript drafting were performed by T. Landre and C. Chouaïd. T. Landre, JB. Auliac and C. Chouaïd contributed to the data acquisition and analysis. T. Landre wrote the initial draft of the manuscript. JB. Assié, G Des Guetz, K. Chouahnia, C. Chouaïd, and JB. Auliac critically revised the manuscript. All authors read and approved the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737140.2024.2362889

Additional information

Funding

This paper was not funded.