Lung cancers with NRG1 fusions are pathologically, clinically, and molecularly more heterogeneous than previously recognized, according to findings from the global eNRGy1 registry published in the Journal of Oncology.

The data also indicate that patients with NRG1-positive lung cancers are only modestly responsive to cytotoxic therapy, immunotherapy, and targeted therapies.

The eNRGy1 registry was established to delineate the characteristics of NRG1 fusion-positive lung cancers and elucidate the clinical activity of systemic therapy in a centrally curated real-world database.

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The researchers analyzed data from 110 patients in the registry. The data were contributed by investigators from 22 centers in 9 countries in Europe, Asia, and the United States.

A majority of patients (71%) had nonmetastatic disease at diagnosis, 57% had mucinous adenocarcinoma, and 57% had never smoked. A majority of NRG1 fusions (74%) were identified by RNA-based next-generation sequencing (NGS), and 26% were detected by DNA-based NGS.

Tumor PD-L1 status was known for 46 patients. The majority of tumors had either no expression of PD-L1 (72%, 33/46) or PD-L1 expression below 50% (24%, 11/46). PD-L1 expression of 50% or greater was observed in 4% of tumors (2/46).

The tumor mutational burden (TMB) was low overall. The median TMB was 0.9 mutations/megabase (range, 0-2.6) as measured by MSK-IMPACT.

Among evaluable patients who received platinum doublet-based chemotherapy, the objective response rate (ORR) was 13% (2/15), and the median progression-free survival (PFS) was 5.8 months.

With post-platinum taxane-based chemotherapy, the ORR was 14% (1/7), and the median PFS was 4.0 months. With afatinib, the ORR was 25% (5/20), and the median PFS was 2.8 months.

The ORR was 0% (0/9) with chemoimmunotherapy and 20% (1/5) with immune checkpoint inhibitor monotherapy. The median PFS was 3.3 months and 3.6 months, respectively.

“The activity of cytotoxic, immune, and targeted therapies was disappointing,” the researchers wrote. “Further research examining NRG1-rearranged tumor biology is needed to develop new therapeutic strategies.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Drilon A, Duruisseaux M, Han J-Y, et al. Clinicopathologic features and response to therapy of NRG1 fusion-driven lung cancers: The eNRGy1 global multicenter registry. J Clin Oncol. Published online June 02, 2021. doi: 10.1200/JCO.20.03307