Non-small cell lung cancer with EGFR exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes

Abstract

Introduction

EGFR exon 20 insertion mutation-positive non-small cell lung cancer (NSCLC) is rare, has a poor prognosis, and outcomes are not fully established. We describe and evaluate outcomes from real-world and clinical evidence in these patients.

Methods

A systematic literature review (SLR) identified interventional and real-world evidence (RWE) studies reporting clinical outcomes for EGFR exon 20 insertion mutation-positive NSCLC. Meta-analyses were conducted by line of therapy to synthesize pooled survival and response outcomes across RWE. Published evidence from interventional studies was summarized individually.

Results

The SLR identified 23 RWE and 19 original interventional studies. In the meta-analysis of RWE, pooled response and survival outcomes were low for first-line EGFR-tyrosine kinase inhibitors (TKIs) and immuno-oncology (IO) agents. First-line chemotherapy resulted in a pooled ORR 25.7%, pooled PFS 5.6 months, and pooled OS 18.3 months. Pooled outcomes were further reduced in second or later lines (≥2 L): pooled ORR was 5.0%, 3.3%, and 13.9%; pooled PFS was 2.1 months, 2.3 months, and 4.4 months; and pooled OS was 14.1 months, 8.8 months, and 17.1 months (not a pooled result) for EGFR-TKIs, IO agents, and chemotherapy, respectively. Interventional studies reported outcomes for TKIs (mobocertinib, poziotinib, osimertinib, afatinib, CLN-081, DZD9008), a monoclonal antibody (amivantamab), and a heat shock protein 90 inhibitor (luminespib). While there is limited RWE for the recently approved agents mobocertinib and amivantamab, which specifically target exon 20 insertion mutations, interventional evidence supports their potential as effective treatment options.

Conclusions

Conventional treatments used in patients with EGFR exon 20 insertion mutation-positive NSCLC have limited efficacy, though chemotherapy appeared to be associated with better response and survival outcomes than non-exon 20 targeting EGFR-TKIs and IO agents. This supports the need to identify EGFR exon 20 insertion mutations as the availability of new targeted treatments may offer additional therapeutic options to these patients.

Keywords:

• Non-small cell lung cancer
• epidermal growth factor receptor mutation
• exon 20 insertion
• systematic literature review
• meta-analysis

Transparency

Declaration of funding

This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Declaration of financial/other relationships

Christina Soeun Kwon and Anna Forsythe are employees of Cytel, Inc. Huamao Mark Lin, Victoria Crossland, and Eileen Curran are employees of Takeda Development Center Americas. Eric N. Churchill is an employee of Takeda Pharmaceuticals USA, Inc. Dimitrios Tomaras is an employee of Purple Squirrel Economics, a wholly owned subsidiary of Cytel, Inc. Sai-Hong Ignatius Ou has received honoraria as speaker bureau of Roche/Genentech, Pfizer, consulting fees from, Pfizer, Roche/Genentech, Astra Zeneca, Takeda/ARIAD, Daiichi Sankyo, Janssen/JNJ, is on the Scientific Advisory Board of Elevation Oncology, Inc., is a former member of the Scientific Advisory board of Turning Point Therapeutics, has stock ownership in Turning Point Therapeutics, Inc., is a current member of the Scientific Advisory board of Elevation Oncology, and has stock ownership in Elevation Oncology. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

Writing assistance was provided by Leah Wiltshire of Cytel, Inc. and funded by Takeda Pharmaceuticals USA, Inc.