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Fusion events involving NRG-1, a member pan-HER pathway, have been highlighted as potential therapeutic target; however, little is known about epidemiological distribution and prognostic value of NRG alterations in large real-world datasets. Data from from 592 patients with newly diagnosed ANSCLC undergone to CGP with DNA and RNA-based NGS (TSO500) from Jan 2020 to Oct 2023 were retrospectively collected in the context of the FPG500 program (interventional monocentric prospective study, NCT06020625). CGP analysis reported NRG-1 alterations in 58 samples (9.7%), including 32 deletions (5,4%), 23 sequence variants (3,8%), 1 NRG-fusion (0,1%), 2 amplifications (0,3%). NRG-1 alterations occurred together with other RTK-KRAS pathway events in 47 samples (81%) and/or with TP53 or BRCA/BRCA2 loss of function in 43 samples (74%). At the time of diagnosis, the median age was 68 y.o. Four pts (7%) had stage III disease and fifty-four (93%) pts had stage IV disease (median N° of metastatic sites = 1.5). Based on clinical evaluation, 40 pts (69%) were eligible for at least 1L treatment. The median 1L-PFS was 11.99 mo. (95%CI; 5.85 – 13.53) and the median OS was 20.26 mo. (95%CI: 11.30 – 24.60). Concurrent TP53 mutations did not resulted in statistically significant association (m1L-PFS p = 0.36; mOS: p = 0.57). In our cohort, NRG-1 alterations resulted frequently associated with poor prognosis and main oncogene alterations and/or loss of function of oncosuppressor genes. Further investigations are needed.
Vita et al. (Fri,) studied this question.