Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With Urothelial Carcinoma Treated With Immune Inhibitor

被引：5

作者：

Bakaloudi, Dimitra Rafailia ^{[1
]}

Talukder, Rafee ^{[2
]}

Makrakis, Dimitrios ^{[3
]}

Diamantopoulos, Leonidas ^{[4
]}

Enright, Thomas ^{[5
]}

Leary, Jacob B. ^{[5
]}

Patgunarajah, Ubenthira ^{[6
]}

Thomas, Vinay M. ^{[7
]}

Swami, Umang ^{[7
]}

Agarwal, Neeraj ^{[7
]}

Jindal, Tanya ^{[8
]}

Koshkin, Vadim S. ^{[8
]}

Brown, Jason R. ^{[9
]}

Barata, Pedro ^{[9
]}

Murgic, Jure ^{[10
,11
]}

Miletic, Marija ^{[10
]}

Johnson, Jeffrey ^{[12
]}

Zakharia, Yousef ^{[12
]}

Hui, Gavin ^{[13
]}

Drakaki, Alexandra ^{[13
]}

Duran, Ignacio ^{[14
]}

Buznego, Lucia A. ^{[14
]}

Barrera, Rafael M. ^{[15
]}

Castaneda, David M. ^{[15
]}

Rey-Cardenas, Macarena ^{[16
]}

Castellano, Daniel ^{[16
]}

Nguyen, Charles B. ^{[17
]}

Park, Joseph J. ^{[17
]}

Alva, Ajjai ^{[17
]}

McKay, Rana R. ^{[18
]}

Stewart, Tyler F. ^{[18
]}

Epstein, Ilana B. ^{[19
]}

Bellmunt, Joaquim ^{[19
]}

Wright, Jonathan L. ^{[20
]}

Gupta, Shilpa ^{[6
]}

Grivas, Petros ^{[1
,21
]}

Khaki, Ali Raza ^{[22
]}

机构：

[1] Univ Washington, Dept Med, Div Hematol & Oncol, Seattle, WA USA

[2] Baylor Coll Med, Dept Med, Div Hematol Oncol, Houston, TX USA

[3] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, Bronx, NY USA

[4] Mayo Clin, Dept Hematol & Oncol, Rochester, MN USA

[5] Univ Washington, Dept Med, Seattle, WA USA

[6] Cleveland Clin Fdn, Taussig Canc Inst, Dept Hematol & Oncol, Cleveland, OH USA

[7] Univ Utah, Dept Med, Div Oncol, Salt Lake City, UT USA

[8] Univ Calif San Francisco, Helen Diller Family Canc Ctr, Dept Med, Div Hematol Oncol, San Francisco, CA USA

[9] Univ Hosp Seidman Canc Ctr, Div Hematol & Oncol, Cleveland, OH USA

[10] Sestre Milosrdnice Univ Hosp Ctr, Dept Oncol & Nucl Med, Zagreb, Croatia

[11] Catholic Univ, Croatia Sch Med, Zagreb, Croatia

[12] Univ Iowa, Dept Med, Div Oncol, Iowa City, IA USA

[13] UCLA, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA USA

[14] Univ Hosp Marques Valdecilla, Dept Oncol, Cantabria, Spain

[15] Univ Autonomade Barcelona, Va dHebron Univ Hosp, Va dHebron Inst Oncol, Dept Med Oncol, Barcelona, Spain

[16] Hosp Univ 12 Octubre, Dept Med Oncol, Madrid, Spain

[17] Univ Michigan, Dept Med, Div Oncol, Ann Arbor, MI USA

[18] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA

[19] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA

[20] Univ Washington, Dept Urol, Seattle, WA USA

[21] Fred Hutchinson Canc Ctr, Clin Res Div, Seattle, WA USA

[22] Stanford Univ, Dept Med, Div Oncol, Palo Alto, CA USA

来源：

CLINICAL GENITOURINARY CANCER | 2024年 / 22卷 / 06期

关键词：

Immunotherapy; Biomarkers; Bladder cancer; Genomics; Urothelial carcinoma; CISPLATIN-INELIGIBLE PATIENTS; 1ST-LINE PEMBROLIZUMAB; ENFORTUMAB VEDOTIN; CHEMOTHERAPY CHEMO; CLINICAL-OUTCOMES; SINGLE-ARM; CANCER; ATEZOLIZUMAB; BIOMARKER; MUC;

D O I：

10.1016/j.clgc.2024.102198

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Based on published data, Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with response and survival in patients with advanced urothelial carcinoma treated with ICI in a "real-world" setting. High TMB and MSI were associated with better outcomes consistent with prior data. Background: Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI. Methods: Patients from 15 institutions were treated with ICI monotherapy. Primary endpoint was overall survival and secondary endpoints included observed response rate (ORR), and progression-free (PFS) calculated from ICI initiation. TMB was analyzed as dichotomous ( >= 10 vs. < 10 mut/Mb) and continuous variable. Results: We identified 411 patients: 203 were treated with ICI 1L/upfront; 104 with 2 + L. For the 1L/upfront: median [m] OS was numerically longer in patients with TMB >= 10 versus TMB < 10: mOS 35 versus 26 months (HR = 0.6) and with MSI-H and MSI-S (mOS NR vs. 22 months), though neither association was statistically significant. A statistically significant association was found between TMB (continuous variable) and OS (HR = 0.96, P = .01). For 2 + L: mOS was numerically longer in patients with TMB >= 10 versus TMB < 10: (20 vs. 12 months; HR = 0.9); mOS was 12 and 17 months for patients with MSI-H and MSI-S, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB >= 10 versus TMB < 10: 61 versus 17 months; (HR = 0.2, P = .02) and with MSI-H and MSI-S (NR vs. 24 months). Conclusions: Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed.

引用

页数：14

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