NRG1 fusion-driven cancers: A systematic literature review and meta-analysis.

Abstract

e15605 Background: Neuregulin 1 (NRG1) fusion proteins have recently been identified as oncogenic drivers in diverse cancers with high unmet medical need. We recently reported promising responses in patients with cancers harboring NRG1 fusions treated with the bispecific antibody MCLA-128 (Schram 2019). The objective of this study was for the first time to quantitatively summarize the frequency of tumors harboring NRG1 fusions reported in the published literature. Methods: Neuregulin 1 (NRG1) fusion proteins have recently been identified as oncogenic drivers in diverse cancers with high unmet medical need. We recently reported promising responses in patients with cancers harboring NRG1 fusions treated with the bispecific antibody MCLA-128 (Schram 2019). The objective of this study was for the first time to quantitatively summarize the frequency of tumors harboring NRG1 fusions reported in the published literature. Results: Out of 212 articles identified in the literature as of 31-Jul-2019, 37 met the inclusion criteria and were abstracted. 13 different tumor types were identified as harboring NRG1 fusions including 5 tumor (sub)types which met the criteria for frequency meta-analysis (Table 1). NRG1 fusions were most frequent in pancreatic adenocarcinoma (3.3%, 95% confidence intervals (CI): 0.3-28.7%; apparent enrichment in KRAS WT) and NSCLC (0.8% 95% CI: 0.3-2.7%) with an enrichment in invasive mucinous adenocarcinoma (9.8%, 95% CI: 4.7-19.6%). Statistically significant heterogeneity was observed indicating substantial variation across studies in each analysis. For tumor types that did not meet the criteria for meta-analysis (uterine, renal cell, ovarian, colorectal, head and neck, bladder, prostate and sarcoma) the reported frequency of NRG1 fusions was typically less than 1%. Conclusions: NRG1 fusions are present across a wide range of different solid tumor types, most frequently in NSCLC and PDAC. NRG1 fusion-driven cancers represent a potential tumor-agnostic therapeutic target. The advent of new treatment options and increased genomic testing will allow a more precise estimation of the frequency of NRG1 fusions in cancer. [Table: see text]