Issues

Drilon and colleagues identified a patient with NRG1-rearranged invasive mucinous adenocarcinoma who achieved an exceptional response to an anti-ERBB3 monoclonal antibody, whereas ERBB2 inhibition did not achieve responses in four patients with NRG1-rearranged lung cancer, suggesting that ERBB3 inhibition may be more effective in this patient population In vitro, NRG1-rearranged cell lines were sensitive to inhibition of either ERBB2 or ERBB3, but in vivo, ERBB3 inhibition produced durable tumor regression, whereas ERBB2 inhibition had less pronounced antitumor activity Analysis of 26,469 tumors from The Cancer Genome Atlas and MSK-IMPACT revealed NRG1 rearrangements at low frequency in a variety of tumors, supporting a basket trial design for the investigation of ERBB3-targeted therapies in patients with NRG1-rearranged tumors For details, please see the article by Drilon and colleagues on page 686.