We characterized the clinical and genomic features of MTAPdef mUC in 193 patients treated at MD Anderson Cancer Center (MDACC) and 298 patients from the phase 2 IMvigor210 trial, which investigated atezolizumab in cisplatin-ineligible and platinum-refractory disease. In the MDACC cohort, visceral metastases were significantly more common for MTAPdef (n = 48) than for MTAP-proficient (MTAPprof; n = 145) patients (75% vs 55.2%; p = 0.02). MTAPdef was associated with poor prognosis (median overall survival [mOS] 12.3 vs 20.2 mo; p = 0.007) with an adjusted hazard ratio of 1.93 (95% confidence interval 1.35–2.98). Similarly, IMvigor210 patients with MTAPlo (n = 29) had a higher incidence of visceral metastases than those with MTAPhi tumors (n = 269; 86.2% vs 72.5%; p = 0.021) and worse prognosis (mOS 8.0 vs 11.3 mo; p = 0.042). Hyperplasia-associated genes were more frequently mutated in MTAPdef tumors (FGFR3: 31% vs 8%; PI3KCA: 31% vs 19%), while alterations in dysplasia-associated genes were less common in MTAPdef tumors (TP53: 41% vs 67%; RB1: 0% vs 16%). Our findings support a distinct biology in MTAPdef mUC that is associated with early visceral disease and worse prognosis.
Patient summary:
We investigated the outcomes for patients with the most common gene loss (MTAP gene) in metastatic cancer of the urinary tract. We found that this loss correlates with worse prognosis and a higher risk of metastasis in internal organs. There seems to be distinct tumor biology for urinary tract cancer with MTAP gene loss and this could be a potential target for treatment.
Omar Alhalabi,1 Yueting Zhu,1,2 Ameer Hamza,3 Wei Qiao,4 Yiyun Lin,5 Raymond M. Wang,1 Amishi Y. Shah,1 Matthew T. Campbell,1 Vijaykumar Holla,6 Ashish Kamat,7 Wei-Lien Wang,3 Jennifer Wang,1 Jianfeng Chen,1 Jieru Meng,1 Miao Zhang,3 Jolanta Bondaruk,3 Mark Titus,1 Giannicola Genovese,1 Bogdan A. Czerniak,3 Kenna R. Shaw,5 Funda Meric-Bernstam h,8 Charles C. Guo,3 Christopher J. Logothetis,1 Arlene Siefker-Radtke,1 Pavlos Msaouel,1 Linghua Wang h,7 Jiyan Liu,2 Jianjun Gao1
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Biotherapy, Cancer Center and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA