Key Points
• In the current case report, authors detail clinical outcomes of a 71-year-old non-smoker with RET-fusion NSCLC who is treated with frontline pembrolizumab. OF note, the patient exhibited brain, liver, and bone metastases. The patient was in complete tumor response at 29 months following pemrolizumab initiation. The patient also received whole brain radiation therapy and steroid treatments.
• In 1%-2% of NSCLC patients, RET rearrangement is demonstrated. It typically occurs among non-smokers and is linked to an increased risk of brain metastasis. The best frontline therapy remains to be elucidated, with selpercatinib and pralsetinib exhibiting activity. “To our knowledge, this is the first report of a favorable outcome following ICI as a frontline therapy for RET-rearranged NSCLC. Some studies of ICI, mostly as treatment in subsequent lines, do not suggest a favorable result,” the authors wrote.
• Although this paper may be limited in its generalizability, per the authors, it does support the use of ICI for RET-rearranged NSCLC. “Given the familiarity of clinicians to EGFR- or ALK-altered NSCLC in which ICI should be avoided, the evidence of durable and profound response to frontline ICI in RET-rearranged NSCLC suggests that these tumors may be biologically different in the mechanism of resistance to ICI. Thus, ICI without chemotherapy should remain under consideration as a frontline therapeutic option for RET-rearranged NSCLC, especially when PD-L1 expression is elevated,” the authors wrote.