Immunotherapy-based therapy as a promising treatment for EGFR-mutant advanced non-small cell lung cancer patients after EGFR-TKI resistance

ABSTRACT

Introduction

Traditionally, epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) has been regarded as a cold tumor based on the immunosuppressive tumor immune microenvironment (TIME). However, recent studies have found that EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment could shift host immunity from immunosuppressive to immunosupportive TIME, which has renewed hopes of immunotherapy.

Areas covered

In this review, we highlight five main immunotherapy-based therapies for patients after EGFR-TKI failure, including safety and efficacy data from prospective and retrospective clinical studies.

Expert opinion

The efficacy of immunotherapy alone is extremely limited. Immunotherapy plus chemotherapy show an ORR of 29.5%–59.3% and an mPFS of about 7 months. There is still scarce evidence for immunotherapy plus antiangiogenesis therapy. A combination of immunotherapy with EGFR-TKIs exhibits higher treatment-related adverse events and lower clinical outcomes compared to EGFR-TKI alone. Importantly, immunotherapy plus antiangiogenesis and chemotherapy achieves an mPFS of 6.9–10.2 months. In general, the strategy of combining immunotherapy with chemotherapy and/or an antiangiogenic drug is a novel and promising method for treating advanced NSCLC after EGFR-TKI failure. Therefore, the dominant population of EGFR-TKI resistant patients were characterized by EGFR uncommon mutation, EGFR L858R mutation, PD-L1 ≥ 50%, prior antiangiogenic drugs, and negative T790 M mutation for immunotherapy-based therapy.

KEYWORDS:

• Immunotherapy
• EGFR mutation
• non-small cell lung cancer
• tyrosine kinase inhibitor
• drug resistance

Article highlights

• EGFR-TKI treatment could change the original immunosuppressive status of EGFR-mutant NSCLC patients into an immunosupportive tumor immune microenvironment (TIME), which renews the hope of immunotherapy.

• For EGFR-TKI-resistant patients with NSCLC, the combination of immunotherapy plus chemotherapy and (or) antiangiogenesis represents a novel and promising strategy.

• The NSCLC patients with EGFR uncommon mutation, EGFR L858R mutation, PD-L1≥50%, and prior antiangiogenic drugs and negative T790M mutation may benefit more from immunotherapy-based therapy after EGFR-TKI failure.

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.

Additional information

Funding

This paper received funding from the Key project of Jiangxi Natural Science Foundation (No. 20224ACB206038), China.