2198P - Clinicopathologic characteristics and outcomes to immune checkpoint inhibitor therapy in patients with HER2-altered metastatic non-small cell lung cancer

Background

ERBB2 (HER2) alterations are found in up to 4% of patients with non-small cell lung cancer (NSCLC), and associate with poor prognosis. Although chemo-immunotherapy is used in the first-line setting for these patients, the role of immune checkpoint inhibitor (ICI) therapy alone remains limited. We sought to characterize the clinicopathologic features of patients with HER2 alterations and their outcomes to ICI therapy.

Methods

We conducted a retrospective analysis of patients with advanced NSCLC treated with PD-L1 inhibitors with or without CTLA-4 inhibition at the Dana-Farber Cancer Institute. Clinicopathologic characteristics and clinical outcomes of patients with HER2 alterations were reviewed and compared to patients with classical EGFR mutations (L858R and Exon 19 deleted).

Results

We identified 23 patients with HER2 alterations and 80 with classical EGFR mutations treated with ICI therapy alone. Median age of patients with HER2 alterations was similar to patients with classical EGFR alterations (57 vs 62, P=0.2). Patients with HER2 alterations were predominantly female (83%, N=19) and had no history of tobacco use (57%, N=13). Compared to patients with EGFR alterations, patients with HER2 alterations had similar tumor mutational burden (median 8.0 vs 8.4 mut/Mb, P=0.6), PD-L1 tumor proportion score (TPS, median 10% vs 60%, P=0.7), and poor objective response rates to ICI therapy (8.7% vs 3.8%, P=0.3). Two patients with HER2 Exon 20 insertions achieved a partial response, both were female with no smoking history, PDL1 TPS score of ≥50%, and received treatment in the second-line setting. Median progression-free survival to ICI therapy in patients with HER2 alterations was similar to patients with classical EGFR alterations [2.1 vs 1.5 months, respectively, HR 0.7, P=0.2], as was overall survival [9.0 vs 4.5 months, respectively, HR 0.7, P=0.1].

Conclusions

In comparison to patients with classical EGFR alterations, those with HER2 alterations and advanced NSCLC have similar poor outcomes to treatment with ICI therapy. A comprehensive analysis of the tumor immune microenvironment may provide insight into future biomarkers of response.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

B. Ricciuti: Financial Interests, Personal, Advisory Board: Regeneron. P.A. Jänne: Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Eli Lilly, Voronoi, Daiichi Sankyo, Novartis, Sanofi, Takeda Oncology, Mirati Therapeutics, Transcenta, Silicon Therapeutics, Syndax, Nuvalent, Bayer, Eisai, Allorion Therapeutics, Accutar Biotech, AbbVie, Duality Biologics; Financial Interests, Personal, Advisory Board, Consulting fees for advice on diagnostic development: Biocartis; Financial Interests, Personal, Advisory Board, Consulting fee for advice on drug development: Merus, Frontier Medicines; Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development: Hongyun Biotechnology; Financial Interests, Personal, Stocks/Shares: Gatekeeper Pharmaceuticals, Allorion Therapeutics; Financial Interests, Personal, Royalties, I receive post-marketing royalties from being an inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp: Lab Corp; Financial Interests, Institutional, Research Grant, Sponsored research agreement with my institution: AstraZeneca, Daiichi Sankyo, PUMA, Eli Lilly, Boehringer Ingelheim, Revolution Medicines, Takeda Oncology. M.M. Awad: Financial Interests, Personal, Advisory Board: Merck, Bristol Myers Squibb, Genentech, AstraZeneca, Nektar, Maverick, Blueprint Medicine, Syndax, AbbVie, Gritstone, ArcherDX, Mirati, NextCure, EMD Serono; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Lilly, Genentech, AstraZeneca. J.K. Rotow: Financial Interests, Personal and Institutional, Principal Investigator: AbbVie, AstraZeneca, BioAtla, Loxo/Lilly; Financial Interests, Personal and Institutional, Advisory Role: AbbVie; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, BioAtla, Loxo/Lilly; Financial Interests, Personal, Advisory Board: G1 Therapeutics, Genentech, Guardant, Janssen, Sanofi, Summit, Takeda; Financial Interests, Personal, Advisory Role: Gritstone Oncology; Financial Interests, Institutional, Principal Investigator: Bicycle Therapeutics, Blueprint, Daiichi Sankyo, Enliven, EpimAb, ORIC, Redcloud. All other authors have declared no conflicts of interest.