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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
RET fusion lung cancer is a rare adenocarcinoma driven by a fused RET gene. The selective pill selpercatinib shrinks most tumours and more than doubles the time to progression compared with chemotherapy and immunotherapy, and pralsetinib is a second option.
RET fusions were found in lung cancer in 2012, but the first drugs tried, the multikinase inhibitors cabozantinib and vandetanib, produced responses in fewer than a third of patients with heavy off-target toxicity. Selective RET inhibitors designed from 2014 onward changed that: in LIBRETTO-001 selpercatinib produced a 64 percent response rate in patients who had received platinum chemotherapy and 85 percent in treatment-naive patients, with intracranial responses in most patients with measurable brain disease, and it received accelerated approval in May 2020. Pralsetinib followed in September 2020 on the ARROW study, with response rates of 61 percent after platinum and 70 percent in treatment-naive patients.
LIBRETTO-431 (2023) was the randomised confirmation: selpercatinib against platinum-pemetrexed with or without pembrolizumab first line gave median progression-free survival of 24.8 versus 11.2 months (hazard ratio 0.46) and far fewer brain progressions, so selective RET inhibition became the first-line standard. Side effects are hypertension, liver enzyme rises, dry mouth, oedema and, rarely, hypersensitivity; QT prolongation is monitored. Checkpoint inhibitors work poorly in RET fusion disease.
| Setting | Approach | Guideline |
|---|---|---|
| Advanced, first line | Selpercatinib (LIBRETTO-431) as preferred; pralsetinib as an alternative. | not mapped |
| Advanced, after a RET inhibitor | Platinum-pemetrexed with or without pembrolizumab; clinical trial of a next-generation RET inhibitor; local radiotherapy for oligoprogression. | not mapped |