74MO - Impact of MTAP loss on prognosis and efficacy of immune check point inhibitors across advanced solid tumors: SCRUM-Japan MONSTAR-SCREEN-1

Background

Methylthioadenosine phosphorylase (MTAP) is vital for methionine salvage and functions as a tumor suppressor. Although MTAP loss is observed in approximately 15% of solid tumors, the clinicopathological significance of MTAP loss remains unclear.

Methods

The SCRUM-Japan MONSTAR-SCREEN-1 study, a nationwide cancer genome screening project focusing on patients (pts) with advanced solid tumors in Japan, analyzed blood and tissue samples using comprehensive genomic profiling (CGP). MTAP loss was assessed using CGP with FoundationOne®︎ CDx (Foundation Medicine, Inc., Cambridge, MA, USA). The study investigated the association between MTAP loss and clinicopathological characteristics, including prognosis and treatment efficacy.

Results

Of the 773 pts with solid tumors successfully analyzed using tissue CGP in the MONSTAR-SCREEN-1, 71 (9.2%) harbored MTAP loss, particularly in pancreatic (36.1%), urothelial (34.5%), biliary tract (19%), malignant melanoma (10.6%), gastric (9.5%), and head and neck cancers (9.2%). No significant differences were observed in clinicopathological characteristics, such as age, gender, histology, primary tumor location, and metastatic sites between MTAP loss and wild-type groups across cancer types, with the exception of a higher prevalence of MTAP loss in nasopharynx and hypopharynx among head and neck cancer. CDKN2A and CDKN2B were significantly co-altered in pts with MTAP loss across cancer types, excluding malignant melanoma. In urothelial cancer, pts with MTAP loss had significantly lower overall survival (OS) rates than those without (hazard ratio [HR]: 6.98, 95% CI: 1.43-34.00). This trend of inferior OS in the MTAP loss group was consistently observed across all cancer types, except pancreatic cancer. Furthermore, MTAP loss was significantly associated with shorter progression-free survival in pts treated with immune checkpoint inhibitors (ICIs) (HR: 1.77, 95% CI: 1.12-2.83).

Conclusions

MTAP loss is associated with worse prognosis and reduced efficacy of ICIs in pts with advanced solid tumors, highlighting the necessity for the development of novel therapeutic strategies for this specific group.

Clinical trial identification

Editorial acknowledgement

During the preparation of this work, the author used GPT-4.0/Open AI for English editing. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Legal entity responsible for the study

National Cancer Center East.

Funding

Has not received any funding.

Disclosure

T. Fujisawa: Financial Interests, Personal, Invited Speaker: Amelieff Co Ltd.. S. Ikeda: Financial Interests, Personal, Invited Speaker: Guardant Health, Chugai Pharmaceutical Co., Ltd., MSD, Bayer Pharmaceutical, AstraZeneca, Novartis, BMS, ACT Genomics, Roche, ACT Med; Financial Interests, Institutional, Research Funding: Foundation Medicine, ACT Genomics, Canon Medical, Hitachi Systems; Financial Interests, Personal, Speaker, Consultant, Advisor: Illumina. S. Kadowaki: Financial Interests, Personal, Invited Speaker: Taiho, MSD, Ono, Daiichi Sankyo, BMS, Bayer, Merck, Eisai, Otsuka; Financial Interests, Institutional, Funding: Eli Lilly, MSD, Ono, Daiichi Sankyo, Chugai, Nobelpharma, Yansen. C. Morizane: Financial Interests, Personal, Advisory Board: Yakult, MSD, Servier, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Merck biopharma; Financial Interests, Personal, Invited Speaker: Novartis, Teijin Pharma; Financial Interests, Institutional, Coordinating PI: Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical, Eisai, MSD K.K., J-Pharma, AstraZeneca, Merck biopharma; Financial Interests, Institutional, Funding: Daiichi Sankyo RD Novare, Hitachi. M. Ueno: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Incyte, MSD, Nihon Servier, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, J-pharma, Eisai, Yakult Honsha; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Local PI: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, DFP, Daiichi Sankyo, Eisai, Incyte, MSD, Merck Biopharma, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis, J-pharma, Novocure, Chiome Bioscience. E. Oki: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly, Bristol Myers Squibb, MSD, Takeda Pham; Financial Interests, Institutional, Research Grant: Guardant Health. S. Yuki: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Taiho Pharmaceutical Co., Ltd, Bristol Myers Squibb K.K., Ono Pharmaceutical Co., Ltd, Takeda Parmaceutical Co.,Ltd., MSD K.K., Merck Biopharma Co., Ltd., Bayer Yakuhin Ltd., MIYARISAN Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Role: Chugai Pharmaceutical Co., Ltd.. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Sanofi; Financial Interests, Personal, Invited Speaker: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Pfizer, Sanofi, Taiho; Financial Interests, Personal and Institutional, Steering Committee Member: Chugai, Daiichi Sankyo, AstraZeneca, MSD, Amgen, Sanofi, Novartis, Pfizer, Kyowa Hakko Kirin; Financial Interests, Personal and Institutional, Local PI: Lilly, Bayer, Behringer, Nihon Kayaku. S. Okano: Financial Interests, Personal, Invited Speaker: MSD, Merck Biophama Co.,Ltd., Ono Pharmaceutical CO., LTD., Bristol Myers Squibb. K. Namikawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Novartis Pharma, MSD, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Novartis Pharma, MSD. H. Bando: Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Other, Lecture fee: Ono pharmaceutical, Taiho pharmaceutical, Eli Lilly Japan. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd, Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., FALCO Biosystems Ltd., Merus N.V., Bristol Myers Squibb K.K., Medical & Biological Laboratories Co., LTD., Takeda Pharmaceutical Co., Ltd.. Y. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Guardant Health AMEA; Financial Interests, Institutional, Funding: Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Roche Diagnostics; Financial Interests, Institutional, Coordinating PI: Seagen. All other authors have declared no conflicts of interest.