INTUITT-NF2: brigatinib in NF2-related schwannomatosis with progressive tumours
In people with the inherited condition NF2 whose nerve and brain-lining tumours were growing despite earlier treatment, the kinase inhibitor brigatinib shrank some tumours, slowed the growth of all types and improved hearing in a third of affected ears without serious toxicity.
Overview
First sub-study of the adaptive platform trial INTUITT-NF2: 40 patients (median age 26) with NF2-related schwannomatosis and progressive target tumours (10 vestibular schwannomas, 8 non-vestibular schwannomas, 20 meningiomas, 2 ependymomas) received brigatinib.
After a median follow-up of 10.4 months, 10 percent of target tumours and 23 percent of all tumours had a radiographic response, with meningiomas and non-vestibular schwannomas benefiting most; annualised growth rates fell for all tumour types; hearing improved in 35 percent of eligible ears; pain scores fell; and there were no grade 4 or 5 treatment-related adverse events.
- Radiographic response in 10 percent (95% CI 3 to 24) of target tumours and 23 percent (16 to 30) of all tumours.
- Annualised growth rates decreased for every tumour type during treatment.
- Hearing improvement in 35 percent (95% CI 20 to 53) of eligible ears; no grade 4 or 5 treatment-related adverse events.
Brigatinib is the first drug shown to act across the tumour types of NF2-related schwannomatosis and is now offered for progressive tumours; the platform design lets further drugs be tested against the same benchmark.
- Single-arm sub-study with short follow-up; responses were modest by size criteria.
- Vestibular schwannomas responded less than meningiomas and non-vestibular schwannomas.
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