Atezolizumab monotherapy for metastatic urothelial carcinoma: final analysis from the phase II IMvigor210 trial

被引：0

作者：

Rosenberg, J. E. ^{[1
]}

Galsky, M. D. ^{[2
]}

Powles, T. ^{[3
]}

Petrylak, D. P. ^{[4
]}

Bellmunt, J. ^{[5
]}

Loriot, Y. ^{[6
]}

Necchi, A. ^{[7
,8
]}

Hoffman-Censits, J. ^{[9
]}

Perez-Gracia, J. L. ^{[10
]}

van der Heijden, M. S. ^{[11
]}

Dreicer, R. ^{[12
]}

Duran, I. ^{[13
,24
]}

Castellano, D. ^{[14
]}

Drakaki, A. ^{[15
]}

Retz, M. ^{[16
]}

Sridhar, S. S. ^{[17
]}

Grivas, P. ^{[18
,19
,20
]}

Yu, E. Y. ^{[19
,20
]}

O'Donnell, H. ^{[21
]}

Burris, H. A. ^{[22
]}

Mariathasan, S. ^{[23
]}

Shi, Y. ^{[23
]}

Goluboff, E. ^{[23
]}

Bajorin, D. ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA

[2] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[3] Queen Mary Univ London ECMC, Barts Canc Inst, Barts Hlth, London, England

[4] Yale Canc Ctr, New Haven, CT USA

[5] Harvard Med Sch, Dana Farber Canc Inst, PSMAR IMIM Lab, Boston, MA USA

[6] Univ Paris Sud, Univ Paris Saclay, Gustave Roussy, Villejuif, France

[7] Univ Vita Salute San Raffaele, Milan, Italy

[8] IRCCS San Raffaele Hosp, Milan, Italy

[9] Johns Hopkins, Baltimore, MD USA

[10] Clin Univ Navarra, Dept Oncol, Pamplona, Spain

[11] Netherlands Canc Inst, Amsterdam, Netherlands

[12] Univ Virginia, Canc Ctr, Charlottesville, VA USA

[13] Hosp Univ Virgen del Rocio, Seville, Spain

[14] Hosp 12 Octubre, Madrid, Spain

[15] Univ Calif Los Angeles, Los Angeles, CA USA

[16] Tech Univ Munich, Munich, Germany

[17] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada

[18] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA

[19] Univ Washington, Seattle, WA USA

[20] Fred Hutchinson Canc Ctr, Seattle, WA USA

[21] Univ Chicago, Chicago, IL USA

[22] Sarah Cannon Res Inst, Nashville, TN USA

[23] Genentech Inc, South San Francisco, CA USA

[24] Hosp Univ Marques Valdecilla, IDIVAL, Santander, Spain

来源：

ESMO OPEN | 2024年 / 9卷 / 12期

关键词：

metastatic urothelial carcinoma; checkpoint inhibitor; long-term survival; PD-L1-high; cisplatin-ineligible; platinum-refractory; PEMBROLIZUMAB; MULTICENTER;

D O I：

10.1016/j.esmoop.2024.103972

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The IMvigor210 trial demonstrated clinical benefit and manageable toxicity with atezolizumab monotherapy [anti-programmed death-ligand 1 (PD-L1)] in patients with metastatic urothelial carcinoma (UC) in primary analyses. Final efficacy and safety results after long-term follow-up are reported. Patients and methods: This phase II single-arm trial of atezolizumab monotherapy in patients with advanced UC included two cohorts: untreated patients ineligible for cisplatin-based chemotherapy (cohort 1; n = 119) and those previously treated with platinum-based chemotherapy (cohort 2; n = 310). Atezolizumab was administered i.v. (1200 mg every 21 days) until progression or unacceptable toxicity. Primary endpoints were independent review facility-assessed confirmed objective response rate (ORR) per RECIST 1.1 in cohort 1 and independent review facility-assessed ORR per RECIST 1.1 and investigator-assessed modified (m)RECIST in cohort 2. Overall survival (OS), efficacy by PD-L1 status, and safety were also assessed. Results: At data cut-off (1 June 2023), the median survival follow-up was 96.4 months (range, 0.2-103.4 months) in cohort 1 and 46.2 months [0.2 (censored)-54.9 months] in cohort 2. In cohort 1, the ORR [95% confidence interval (CI)] was 23.5% (16.2% to 32.2%) in all patients and 28.1% (13.8% to 46.8%) in the PD-L1 tumor-infiltrating immune cell (IC)2/3 subgroup. Median OS (95% CI) was 16.3 months (10.4-24.5 months) overall and 12.3 months (6.0-49.8 months) in the PD-L1 IC2/3 subgroup. In cohort 2, the ORR (95% CI) was 16.5% (12.5% to 21.1%) per RECIST 1.1 and 19.7% (95% CI 15.4% to 24.6%) per mRECIST in all patients and 27.0% (18.6% to 36.8%) and 28.0% (19.5% to 37.9%), respectively, in the PD-L1 IC2/3 subgroup. Median OS (95% CI) was 7.9 months (6.7-9.3 months) in all patients and 11.9 months (9.0-22.8 months) in the IC2/3 subgroup. Treatment-related grade 3/4 adverse events occurred in 21.8% (cohort 1) and 18.7% (cohort 2); one treatment-related death occurred in cohort 1. Conclusions: With long-term follow-up, atezolizumab monotherapy demonstrated clinically meaningful efficacy with durable in a subset of with metastatic UC; there were no new

引用

页数：10

共 24 条

[1]

[Anonymous], 2020, Global Cancer Observatory: Cancer Today

[2] Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma [J].

Bajorin, D. F. ;

Witjes, J. A. ;

Gschwend, J. E. ;

Schenker, M. ;

Valderrama, B. P. ;

Tomita, Y. ;

Bamias, A. ;

Lebret, T. ;

Shariat, S. F. ;

Park, S. H. ;

Ye, D. ;

Agerbaek, M. ;

Enting, D. ;

McDermott, R. ;

Gajate, P. ;

Peer, A. ;

Milowsky, M., I ;

Nosov, A. ;

Antonio Jr, J. N. ;

Tupikowski, K. ;

Toms, L. ;

Fischer, B. S. ;

Qureshi, A. ;

Collette, S. ;

Unsal-Kacmaz, K. ;

Broughton, E. ;

Zardavas, D. ;

Koon, H. B. ;

Galsky, M. D. .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (22) :2102-2114

[3] Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial [J].

Balar, Arjun V. ;

Galsky, Matthew D. ;

Rosenberg, Jonathan E. ;

Powles, Thomas ;

Petrylak, Daniel P. ;

Bellmunt, Joaquim ;

Loriot, Yohann ;

Necchi, Andrea ;

Hoffman-Censits, Jean ;

Perez-Gracia, Jose Luis ;

Dawson, Nancy A. ;

van der Heijden, Michiel S. ;

Dreicer, Robert ;

Srinivas, Sandy ;

Retz, Margitta M. ;

Joseph, Richard W. ;

Drakaki, Alexandra ;

Vaishampayan, Ulka N. ;

Sridhar, Srikala S. ;

Quinn, David I. ;

Duran, Ignacio ;

Shaffer, David R. ;

Eigl, Bernhard J. ;

Grivas, Petros D. ;

Yu, Evan Y. ;

Li, Shi ;

Kadel, Edward E., III ;

Boyd, Zachary ;

Bourgon, Richard ;

Hegde, Priti S. ;

Mariathasan, Sanjeev ;

Thastrom, AnnChristine ;

Abidoye, Oyewale O. ;

Fine, Gregg D. ;

Bajorin, Dean F. .

LANCET, 2017, 389 (10064) :67-76

[4] Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (mUC): Primary analysis of IMvigor210 cohort 1. [J].

Balar, Arjun Vasant ;

Galsky, Matt D. ;

Loriot, Yohann ;

Dawson, Nancy Ann ;

Necchi, Andrea ;

Srinivas, Sandy ;

Joseph, Richard Wayne ;

Vaishampayan, Ulka N. ;

Sridhar, Srikala S. ;

Quinn, David I. ;

Drakaki, Alexandra ;

Duran, Ignacio ;

Rosenberg, Jonathan E. ;

Powles, Thomas ;

Hoffman-Censits, Jean H. ;

Cui, Na ;

Mariathasan, Sanjeev ;

Thastrom, Ann Christine ;

Abidoye, Oyewale O. ;

Bajorin, Dean F. .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (18)

[5] Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study [J].

Bamias, Aristotelis ;

Davis, Ian ;

Galsky, Matthew ;

Arranz, Jose a ;

Kikuchi, Eiji ;

Grande, Enrique ;

Muro, Xavier Garcia del ;

Park, Se Hoon ;

De Giorgi, Ugo ;

Alekseev, Boris ;

Mencinger, Marina ;

Izumi, Kouji ;

Schutz, Fabio A. ;

Puente, Javier ;

Li, Jian-Ri ;

Panni, Stefano ;

Gumus, Mahmut ;

Ozguroglu, Mustafa ;

Mariathasan, Sanjeev ;

Poloz, Yekaterina ;

Bene-Tchaleu, Fabiola ;

Lee, Chooi ;

Bernhard, Sandrine ;

De Santis, Maria .

LANCET ONCOLOGY, 2024, 25 (01) :46-61

[6] Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma [J].

Bellmunt, J. ;

de Wit, R. ;

Vaughn, D. J. ;

Fradet, Y. ;

Lee, J. -L. ;

Fong, L. ;

Vogelzang, N. J. ;

Climent, M. A. ;

Petrylak, D. P. ;

Choueiri, T. K. ;

Necchi, A. ;

Gerritsen, W. ;

Gurney, H. ;

Quinn, D. I. ;

Culine, S. ;

Sternberg, C. N. ;

Mai, Y. ;

Poehlein, C. H. ;

Perini, R. F. ;

Bajorin, D. F. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (11) :1015-1026

[7]

Duran I, 2018, GLOB C BLADD CANC 20

[8] Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3 [J].

Grivas, Petros ;

Pouessel, Damien ;

Park, Chandler H. ;

Barthelemy, Philippe ;

Bupathi, Manojkumar ;

Petrylak, Daniel P. ;

Agarwal, Neeraj ;

Gupta, Sumati ;

Flechon, Aude ;

Ramamurthy, Chethan ;

Davis, Nancy B. ;

Recio-Boiles, Alejandro ;

Sternberg, Cora N. ;

Bhatia, Astha ;

Pichardo, Cabilia ;

Sierecki, Mitch ;

Tonelli, Julia ;

Zhou, Huafeng ;

Tagawa, Scott T. ;

Loriot, Yohann .

JOURNAL OF CLINICAL ONCOLOGY, 2024, 42 (12) :1415-1425

[9] A global, multicentre, open-label, randomised phase II trial of tobemstomig (tobe) with or without tiragolumab (tira) vs atezolizumab (atezo) in patients (pts) with untreated metastatic urothelial cancer (mUC) ineligible for platinumbased chemotherapy (chemo) [J].

Gupta, S. ;

Alhalabi, O. ;

Bamias, A. ;

Bellmunt, J. ;

Castellano Gauna, D. E. ;

Bedke, J. ;

Friedlander, T. ;

Garmezy, B. ;

Grivas, P. ;

Huddart, R. A. ;

Necchi, A. ;

Powles, T. B. ;

Puente, J. ;

Da Rosa, D. A. R. ;

Wang, F. ;

Lambertini, C. ;

Andreev-Drakhlin, A. ;

Fasso, M. ;

Loriot, Y. .

ANNALS OF ONCOLOGY, 2023, 34 :S1225-S1225

[10] IMvigor011: a study of adjuvant atezolizumab in patients with high-risk MIBC who are ctDNA plus post-surgery [J].

Jackson-Spence, Francesca ;

Toms, Charlotte ;

O'Mahony, Luke Furtado ;

Choy, Julia ;

Flanders, Lucy ;

Szabados, Bernadett ;

Powles, Thomas .

FUTURE ONCOLOGY, 2023, :509-515

← 1 2 3 →