Reference Detail

Ref Type

Abstract

PMID

Authors

Title

1132P Regorafenib in Caucasian patients with pretreated advanced KIT-mutant melanoma: A dual center case series

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	35	Supplement 2	September 2024	S743-S744	Ann Oncol

URL

https://www.annalsofoncology.org/article/S0923-7534(24)03654-8/fulltext

Abstract Text

Background Oncogenic KIT-mutations (KITmut) are found in +/- 3% of melanoma patients (pts), most frequently in mucosal (15-21%), acro-lentiginous (11-23%), and melanoma arising on sun-damaged skin (CSDS; 16-27%). Only a minority of pts (20-30%) responds to treatment with small molecule KIT-inhibitors (e.g, imatinib, sunitinib, nilotinib, dasatinib). The activity of regorafenib (REGO, a multi-targeted small molecule inhibitor of KIT, TIE2, VEGFR, PDGFR, RET, RAF, and CSF-1R kinases) has never been studied in a Caucasian population with KIT-mutant melanoma. Methods The outcome of a prospectively identified cohort of advanced KITmut melanoma pts treated with REGO at two medical centers in the EU was investigated (database lock (DBL): 25APR2024). Results Eight patients were included: median age 60.7 years [range 41-76]; Caucasian (100%); AJCC stage IV-M1c: 7 pts, and -M1d: 1 pt; elevated baseline LDH: 3 pts; ECOG performance status 0 and 1: resp. 6- and 2 pts); primary mucosal 2-, acro-lentiginous 3-, and CSDS 3 pts. Oncogenic KITmut were documented in exon 11 (n=5), -13 (n=2), and -17 (n=1). Three pts participated in the prospective REGOMEL phase II clinical trial and 4 pts were treated on a compassionate use basis. All pts were pretreated and had previously progressed on anti-PD-1 and -CTLA-4 based therapy, 3 pts on imatinib. REGO was administered orally, once daily (QD), continuously, at a dose of 40 to 120 mg (n=7), or on a 21/28d regimen of 120 mg QD (n=1). In 7 response evaluable pts, the best overall responses (RECIST v. 1.1) were 1 complete response and 6 partial responses (overall response rate 100%, all responses were confirmed). After a median follow-up of 43w [range 3-65w], treatment and responses were ongoing in respectively 6 and 4 pts. Median duration of response was not reached [range 6-59w]. Median progression free survival was not reached and all pts were alive at DBL. All pts had at least 1 TRAE. Grade 3 TRAE included arterial hypertension, and digestive bleeding (n=1, each). Conclusions REGO demonstrated a manageable safety profile and high anti-tumor activity in this Caucasian population of pretreated advanced KITmut melanoma pts deserving further evaluation in a prospective clinical trial. Legal entity responsible for the study The authors. Funding Bayer

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
KIT act mut	melanoma	predicted - sensitive	Regorafenib	Case Reports/Case Series	Actionable	In a clinical case study, Stivarga (regorafenib) treatment demonstrated safety and preliminary activity in patients with melanoma harboring activating mutations in KIT, resulting in an overall response rate of 100% (7/7, 1 complete and 6 partial responses), with median duration of response and median progression-free survival not reached and response ongoing in 4 patients at a median follow-up of 43 weeks (Ann Oncol (2024) 35 (suppl_2): S743-S744).	detail...