Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer : A Multicenter, Single-Arm, Phase II Trial
PURPOSE: Neoadjuvant gemcitabine and cisplatin (GC) followed by radical cystectomy (RC) is standard for patients with muscle-invasive bladder cancer (MIBC). On the basis of the activity of atezolizumab (A) in metastatic BC, we tested neoadjuvant GC plus A for MIBC.
METHODS: Eligible patients with MIBC (cT2-T4aN0M0) received a dose of A, followed 2 weeks later by GC plus A every 21 days for four cycles followed 3 weeks later by a dose of A before RC. The primary end point was non-muscle-invasive downstaging to < pT2N0.
RESULTS: Of 44 enrolled patients, 39 were evaluable. The primary end point was met, with 27 of 39 patients (69%) < pT2N0, including 16 (41%) pT0N0. No patient with < pT2N0 relapsed and four (11%) with ≥ pT2N0 relapsed with a median follow-up of 16.5 months (range: 7.0-33.7 months). One patient refused RC and two developed metastatic disease before RC; all were considered nonresponders. The most common grade 3-4 adverse event (AE) was neutropenia (n = 16; 36%). Grade 3 immune-related AEs occurred in five (11%) patients with two (5%) requiring systemic steroids. The median time from last dose of chemotherapy to surgery was 7.8 weeks (range: 5.1-17 weeks), and no patient failed to undergo RC because of AEs. Four of 39 (10%) patients had programmed death-ligand 1 (PD-L1)-positive tumors and were all < pT2N0. Of the patients with PD-L1 low or negative tumors, 23 of 34 (68%) achieved < pT2N0 and 11 of 34 (32%) were ≥ pT2N0 (P = .3 for association between PD-L1 and < pT2N0).
CONCLUSION: Neoadjuvant GC plus A is a promising regimen for MIBC and warrants further study. Patients with < pT2N0 experienced improved relapse-free survival. The PD-L1 positivity rate was low compared with published data, which limits conclusions regarding PD-L1 as a predictive biomarker.
| Errataetall: |
CommentIn: J Clin Oncol. 2022 Aug 10;40(23):2656. - PMID 35609220 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
|---|---|
| Enthalten in: |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology - 40(2022), 12 vom: 20. Apr., Seite 1312-1322 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Funt, Samuel A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.04.2022 Date Revised 25.04.2024 published: Print-Electronic ClinicalTrials.gov: NCT02989584 CommentIn: J Clin Oncol. 2022 Aug 10;40(23):2656. - PMID 35609220 Citation Status MEDLINE |
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| doi: |
10.1200/JCO.21.01485 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM336241380 |
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| 100 | 1 | |a Funt, Samuel A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer |b A Multicenter, Single-Arm, Phase II Trial |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 19.04.2022 | ||
| 500 | |a Date Revised 25.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02989584 | ||
| 500 | |a CommentIn: J Clin Oncol. 2022 Aug 10;40(23):2656. - PMID 35609220 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: Neoadjuvant gemcitabine and cisplatin (GC) followed by radical cystectomy (RC) is standard for patients with muscle-invasive bladder cancer (MIBC). On the basis of the activity of atezolizumab (A) in metastatic BC, we tested neoadjuvant GC plus A for MIBC | ||
| 520 | |a METHODS: Eligible patients with MIBC (cT2-T4aN0M0) received a dose of A, followed 2 weeks later by GC plus A every 21 days for four cycles followed 3 weeks later by a dose of A before RC. The primary end point was non-muscle-invasive downstaging to < pT2N0 | ||
| 520 | |a RESULTS: Of 44 enrolled patients, 39 were evaluable. The primary end point was met, with 27 of 39 patients (69%) < pT2N0, including 16 (41%) pT0N0. No patient with < pT2N0 relapsed and four (11%) with ≥ pT2N0 relapsed with a median follow-up of 16.5 months (range: 7.0-33.7 months). One patient refused RC and two developed metastatic disease before RC; all were considered nonresponders. The most common grade 3-4 adverse event (AE) was neutropenia (n = 16; 36%). Grade 3 immune-related AEs occurred in five (11%) patients with two (5%) requiring systemic steroids. The median time from last dose of chemotherapy to surgery was 7.8 weeks (range: 5.1-17 weeks), and no patient failed to undergo RC because of AEs. Four of 39 (10%) patients had programmed death-ligand 1 (PD-L1)-positive tumors and were all < pT2N0. Of the patients with PD-L1 low or negative tumors, 23 of 34 (68%) achieved < pT2N0 and 11 of 34 (32%) were ≥ pT2N0 (P = .3 for association between PD-L1 and < pT2N0) | ||
| 520 | |a CONCLUSION: Neoadjuvant GC plus A is a promising regimen for MIBC and warrants further study. Patients with < pT2N0 experienced improved relapse-free survival. The PD-L1 positivity rate was low compared with published data, which limits conclusions regarding PD-L1 as a predictive biomarker | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a Deoxycytidine |2 NLM | |
| 650 | 7 | |a 0W860991D6 |2 NLM | |
| 650 | 7 | |a atezolizumab |2 NLM | |
| 650 | 7 | |a 52CMI0WC3Y |2 NLM | |
| 650 | 7 | |a Cisplatin |2 NLM | |
| 650 | 7 | |a Q20Q21Q62J |2 NLM | |
| 650 | 7 | |a Gemcitabine |2 NLM | |
| 700 | 1 | |a Lattanzi, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Whiting, Karissa |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Ahmadie, Hikmat |e verfasserin |4 aut | |
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| 700 | 1 | |a Zimmerman, Danielle |e verfasserin |4 aut | |
| 700 | 1 | |a McHugh, Deaglan |e verfasserin |4 aut | |
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| 700 | 1 | |a Durdin, Trey D |e verfasserin |4 aut | |
| 700 | 1 | |a Truong, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Kamradt, Jeffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Khalil, Maged |e verfasserin |4 aut | |
| 700 | 1 | |a Lash, Bradley |e verfasserin |4 aut | |
| 700 | 1 | |a Ostrovnaya, Irina |e verfasserin |4 aut | |
| 700 | 1 | |a McCoy, Asia S |e verfasserin |4 aut | |
| 700 | 1 | |a Hettich, Grace |e verfasserin |4 aut | |
| 700 | 1 | |a Regazzi, Ashley |e verfasserin |4 aut | |
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| 700 | 1 | |a Boswell, Abigail |e verfasserin |4 aut | |
| 700 | 1 | |a Francese, Kaitlyn |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yuanquan |e verfasserin |4 aut | |
| 700 | 1 | |a Folefac, Edmund |e verfasserin |4 aut | |
| 700 | 1 | |a Herr, Harry W |e verfasserin |4 aut | |
| 700 | 1 | |a Donat, S Machele |e verfasserin |4 aut | |
| 700 | 1 | |a Pietzak, Eugene |e verfasserin |4 aut | |
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| 700 | 1 | |a Mortazavi, Amir |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenberg, Jonathan E |e verfasserin |4 aut | |
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