1136P Regorafenib combined with BRAF-/MEK-inhibitors for the treatment of refractory melanoma brain metastases

Onderzoeksoutput: Conference paper


There are no active treatment options for patients (pts) with progressive melanoma brain metastases (MBM) who have failed treatment with immune checkpoint blockade (ICB) and BRAF-/MEK-inhibitors (BRAF/MEKi). Regorafenib (REGO), an oral multi-target kinase inhibitor (incl. inhibition of RAF-dimers), has single-agent activity in pretreated melanoma (VD Mijnsbrugge et al. SMR 2022).
We report our single center retrospective review of prospectively registered pts with refractory MBM treated with REGO and BRAF/MEKi.
17 pts with stage IV-M1d melanoma were included (8F; med age 54y [33-75]; WHO PS: 0/1/2/3 resp. n=3/6/6/2 pts; 13 pts BRAFmt (12 BRAF V600mt, 1 BRAF fusion), 4 pts NRAS Q61mt). All pts previously progressed on ICB, BRAF/MEKi (all BRAFmt pts), chemotherapy (4 pts), T-VEC (2 pts), REGO mono (3 pts), and REGO + ICB (2 pts). At baseline, 15 pts had active MBM (8 pts were on steroids); 4 pts had intracranial evaluable disease only. BRAFmt pts were treated with REGO (40-80 mg QD) combined with BRAF/MEKi, NRASmt pts with REGO + MEKi (+ low-dose BRAFi to mitigate skin toxicity). There were no grade >4 TRAE. Grade 3 TRAE included arterial hypertension (n=4), and hepatotoxicity (n=2). None of the 2 pts without active MBM at baseline progressed intra-cranially. The best objective intracranial response (according to RANO-BM) in 17 response evaluable pts was: PR in 5 pts (29%; incl. 4 BRAFmt pts), and SD in 5 pts (29%; incl. 4 BRAFmt pts). In 5 pts intra- and extracranial disease control (PR, SD) were concordant. 3 pts with PR intra- had SD extra-cranially; 2 pts with SD intra- had PD extra-cranially. Assuming a potential clinical benefit of therapy beyond first PD, 10 out of 16 progressive pts continued treatment and remained clinically stable for an additional 3-48 weeks (w) (median 7w). Median time on REGO+BRAF/MEKi in BRAFmt pts was 13w [range 3-62], and 27.5w [range 3-56] on REGO + MEKi in NRASmt pts. In 3 pts treatment is ongoing (9-62w after initiation). Median PFS and OS is resp. 8.4w and 24.6w in BRAFmt pts; 8.6w and 10.1w in NRASmt pts.
In heavily pretreated patients with refractory MBM, REGO combined with BRAF/MEKi demonstrated promising anti-tumor activity. Further investigation in a prospective trial is warranted.
Originele taal-2English
Pagina's (van-tot)681-681
Aantal pagina's1
TijdschriftAnnals of Oncology
Nummer van het tijdschrift2
StatusPublished - okt 2023
EvenementESMO Congress - Madrid, Spain
Duur: 20 okt 202324 okt 2023


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  • Best poster Award

    Dirven, Iris (Recipient), okt 0202

    Prijs: Prize (including medals and awards)


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