Abstract 80P
Background
Association between bTMB and efficacy of ICIs in advanced solid tumors has not been fully established.
Methods
We collected pretreatment tissue and plasma samples from patients with advanced solid tumors in SCRUM-Japan MONSTAR-SCREEN, a cancer genomic screening consortium in Japan, to enable comprehensive genomic profiling (CGP). Tissue CGP was performed with FoundationOne®CDx; plasma CGP included FoundationOne®Liquid plus a 1.125Mb bTMB assay. Mutational burden was calculated by counting somatic variants (single nucleotide and indels, including synonymous variants, excluding germline and driver mutations) with a qualifying variant allele frequency. The efficacy of anti-PD-1/PD-L1 with or without anti-CTLA4 therapy according to TMB value was evaluated by RECIST v1.1.
Results
bTMB results were available in 426 patients enrolled in MONSTAR-SCREEN as of March 2021; the highest proportion of cancer types were colorectal (23%), followed by breast (13%) and pancreatic cancers (11%). Overall, bTMB-high (bTMB-H; bTMB≥14 muts/Mb) was detected in 21 patients (4.9%). MSI-H co-occurred in 43% (9/21) of bTMB-H tumors. Among 329 patients with both tissue and plasma CGP results (median interval sample collections, 40 days [range 0–5280 days]), a positive correlation between tissue TMB (tTMB) and bTMB was shown, especially in patients (N=109) with an interval between tissue and plasma collections less than 90 days and composite tumor fraction (cTF)≥10％ (r=0.76). In patients who received ICIs (N=195), the objective response rate (ORR) was 40% (2/5), 43% (6/14), and 20% (1/5) in MSI-H, bTMB-H, and tTMB-H patients, respectively. ORR trended higher in bTMB-H than in bTMB-low patients (43% vs. 19%; p=0.05).
Conclusions
Elevated bTMB occurred in approximately 5% of patients with advanced solid tumors. There was positive correlation between bTMB and tTMB in samples collected at a short interval and cTF≥10%. The ORR tended to be higher in bTMB-H patients than in bTMB-low patients, suggesting that bTMB may serve as the potential biomarker for predicting the efficacy of ICIs. Prospective investigation is warranted to clarify clinical utility of bTMB for identifying high TMB tumors that may benefit from ICIs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
SCRUM-Japan.
Disclosure
Y. Nakamura: Financial Interests, Institutional, Research Grant: Genomedia; Financial Interests, Institutional, Research Grant: Guardant Health; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Chugai. S. Kadowaki: Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Merck KGaA; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Chugai Pharma; Financial Interests, Institutional, Research Grant: Nobelpharma. K. Kato: Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Advisory Board: Ono; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: BeiGene; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Ono; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Ono. M. Ueno: Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Yakult Honsha; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Merck Biopharma; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Merck Biopharma; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Research Grant: Chugai. E. Oki: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Takeda Pharmaceutical Co. Ltd. T. Satoh: Financial Interests, Personal and Institutional, Research Grant: Ono pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Yakult Honsha; Financial Interests, Institutional, Research Grant: Giliad; Financial Interests, Institutional, Research Grant: Bristol-Myers; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Yakult Honsha; Financial Interests, Personal, Invited Speaker: Bristol-Myers; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: BeiGene. Y. Komatsu: Financial Interests, Personal, Research Grant: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: TAIHO Phamaceutical Co., Ltd; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: Eli Lilly and Company; Financial Interests, Personal, Research Grant: Mediscience Planning Inc.; Financial Interests, Personal, Research Grant: NanoCarrier Co.,Ltd; Financial Interests, Personal, Research Grant: Yakult; Financial Interests, Personal, Research Grant: Daiichi Sankyo Company, Limited; Financial Interests, Personal, Research Grant: IQVIA Services Japan K.K; Financial Interests, Personal, Research Grant: Japanese Foundation for Multidisciplinary Treatment of Cancer; Financial Interests, Personal, Research Grant: Nationel Cancer Center Japan; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Bayer Yakuhin, Ltd.; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly and Company; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: TAIHO Phamaceutical Co., Ltd. H. Tukachinsky: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine, Inc; Financial Interests, Personal, Stocks/Shares: Roche. J. Lee: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. R. Madison: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche AG. E. Sokol: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. D. Pavlick: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche AG. A. Aiyer: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. D. Fabrizio: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. J. Venstrom: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. G. Oxnard: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. T. Yoshino: Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Merck Biopharma; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Sumitomo Dainippon; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Chigai; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Parexel International; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Sanofi. All other authors have declared no conflicts of interest.