1975P - Systemic therapy for KIT/PDGFRA wild-type GIST

Background

Patients (pts) with metastatic KIT/PDGFRA wild-type (KPWT) gastrointestinal stromal tumours (GIST) usually do not derive any benefit from upfront treatment with imatinib. Most of the studies reported so far include case reports or small series and treatment patterns widely differed according to the medical teams. More studies are therefore needed to define the optimal management of metastatic KPWT GIST pts. The primary aim of this retrospective study was to assess the outcome of pts with KPWT GIST treated by Tyrosine Kinase Inhibitors (TKI) in our institution.

Methods

We conducted a retrospective study at a single institution, the Centre Léon Bérard (CLB). The national sarcoma database (https://netsarc.sarcomabcb.org/) was searched for pts with a diagnosis of KPWT GIST treated at the CLB. Data were extracted from individual patients’ files. All cases were reviewed by an expert sarcoma pathologist. In the absence of a known neurofibromatosis type 1 (NF1) or SDH-deficiency, whole exome-RNAseq was performed on FFPE material.

Results

In total, 86 pts with metastatic KPWT GIST were identified, with a median age at diagnosis of 55 [10-80], a sex-ratio of 0.9 and a median tumor size of 65 mm [11-260]. The primary tumor was in the stomach for 42 pts (49%) and in the duodenum for 40 (47%). The vast majority were KIT and DOG1 positive by IHC (98 and 92%, respectively). Among the 86 pts, 31 (36%) had a metastatic disease, either synchronous (N=15) or metachronous (N=16). The majority of these cases were NF1-associated GIST (N=13, 42%), 7 were SDH-deficient GIST (23%), one was NTRK-rearranged GIST (RBPMS::NTRK3), one harboured TSC1 variant (T314M) and no significant mutation/fusion was detected in 9 GIST. While none of the 31 pts responded to imatinib, 3/3 pts had a partial response with lenvatinib (all SDH-deficient GIST), 1/3 with pazopanib, 2/20 (10%) with sunitinib and 2/10 (20%) with regorafenib. Interestingly, the highest duration of response PFS was with pazopanib (111 months).

Conclusions

This retrospective series of KPWT GIST is one of the largest with this rare disease. Although there was no response to first line TKI imatinib, some long responders are reported with anti-angiogenic TKI and warrant additional investigation through prospective trials to validate those results.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

InfoSarcomes, InterSarc.

Disclosure

M. Brahmi: Financial Interests, Personal, Advisory Board: Bayer, Deciphera; Financial Interests, Personal, Invited Speaker: Amgen. A. Dufresne: Non-Financial Interests, Project Lead, Translational research project: GSK, Adaptimmune; Non-Financial Interests, Project Lead, Translational research program: Bayer. P. Cassier: Financial Interests, Personal, Advisory Board: Merck Serono/EMD, Roche, Amgen, Boehringer ingelheim; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Advisor: Ose Immunotherapeutics; Financial Interests, Institutional, Local PI: AbbVie, Blueprint, Exelixis, GSK, Janssen, Novartis, Roche, Taiho, Loxo/Eli Lilly; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Institutional, Product Samples: Plexxikon, Novartis, MSD, AstraZeneca, GSK. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmun, Eisai, Sutro, BMS, Adaptimmune, Daiichi Sankyo; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: GINECO. J. Blay: Financial Interests, Personal, Advisory Board: Bayer, Deciphera, GSK, Roche; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Invited Speaker: MSD, MSD; Financial Interests, Personal, Other, member of the supervisory board: Innate pharma; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. All other authors have declared no conflicts of interest.