Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial.
Saved in:
| Title: | Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. |
|---|---|
| Authors: | De Santis, Maria (AUTHOR), Palou Redorta, Joan (AUTHOR), Nishiyama, Hiroyuki (AUTHOR), Krawczyński, Michał (AUTHOR), Seyitkuliev, Artur (AUTHOR), Novikov, Andrey (AUTHOR), Guerrero-Ramos, Félix (AUTHOR), Zukov, Ruslan (AUTHOR), Kato, Minoru (AUTHOR), Kawahara, Takashi (AUTHOR), Goeman, Lieven (AUTHOR), Puente, Javier (AUTHOR), Hellmis, Eva (AUTHOR), Powles, Thomas (AUTHOR), Radziszewski, Piotr (AUTHOR), Gust, Kilian M (AUTHOR), Vasey, Paul (AUTHOR), Bigot, Pierre (AUTHOR), Fradet, Yves (AUTHOR), Hunting, Jarmo (AUTHOR) |
| Source: | Lancet. Nov2025, Vol. 406 Issue 10516, p2221-2234. 14p. |
| Subjects: | Non-muscle invasive bladder cancer, BCG immunotherapy, Treatment effectiveness, Adverse health care events, Progression-free survival, Immune checkpoint inhibitors, Clinical trials |
| Abstract: | Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) often have recurrence or progression after transurethral resection of bladder tumour (TURBT) and subsequent BCG therapy. We aimed to evaluate whether 1 year of durvalumab with BCG could improve outcomes versus BCG alone for these patients. This randomised, open-label, phase 3 trial enrolled patients aged 18 years or older with BCG-naive, high-risk NMIBC who underwent TURBT. Patients were randomly allocated (1:1:1) to receive intravenous durvalumab (every 4 weeks for 13 cycles) plus intravesical BCG induction (weekly for 6 weeks) and maintenance (three doses at weekly intervals at 3, 6, 12, 18, and 24 months), durvalumab plus BCG induction, or BCG induction and maintenance (comparison group). The primary endpoint was investigator-assessed disease-free survival in the durvalumab plus BCG induction and maintenance group versus the comparison group in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT03528694) and EudraCT (2017-002979-26) and is ongoing but is no longer enrolling patients. Between June 18, 2018, and Oct 2, 2020, 1350 patients were assessed for eligibility, among whom 1018 patients were randomly allocated: 339 to the durvalumab plus BCG induction and maintenance group (of whom 336 [99%] initiated and 180 [53%] completed treatment), 339 to the durvalumab plus BCG induction group (337 [99%] initiated and 239 [71%] completed treatment), and 340 to the comparison group (339 [>99%] initiated and 182 [54%] completed treatment). At a median follow-up of 60·7 months (IQR 51·5–66·5), there were 67 (20%) disease-free survival events in the durvalumab plus BCG induction and maintenance group and 98 (29%) events in the comparison group, resulting in a 32% reduction in the risk of recurrence of high-risk disease or death by any cause with durvalumab plus BCG induction and maintenance versus the comparison group (hazard ratio 0·68 [95% CI 0·50–0·93]; log-rank p=0·015). Among patients who received at least one dose of study treatment, grade 3 or 4 treatment-related adverse events occurred in 71 (21%) of 336 patients in the durvalumab plus BCG induction and maintenance group, 52 (15%) in the durvalumab plus BCG induction only group, and 13 (4%) of 339 patients in the comparison group. No treatment-related adverse events led to death. Among patients with BCG-naive, high-risk NMIBC, 1 year of durvalumab combined with BCG induction and maintenance therapy showed a statistically significant and clinically meaningful improvement in disease-free survival versus BCG induction and maintenance alone. The combination had a manageable safety profile, consistent with that of the individual therapies. These results support 1 year of durvalumab in combination with BCG induction and maintenance therapy as a potential new treatment for this patient population. AstraZeneca. [ABSTRACT FROM AUTHOR] |
| Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Text: Availability: 0 |
|---|---|
| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 189149239 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22De+Santis%2C+Maria%22">De Santis, Maria</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Palou+Redorta%2C+Joan%22">Palou Redorta, Joan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nishiyama%2C+Hiroyuki%22">Nishiyama, Hiroyuki</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Krawczyński%2C+Michał%22">Krawczyński, Michał</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Seyitkuliev%2C+Artur%22">Seyitkuliev, Artur</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Novikov%2C+Andrey%22">Novikov, Andrey</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Guerrero-Ramos%2C+Félix%22">Guerrero-Ramos, Félix</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zukov%2C+Ruslan%22">Zukov, Ruslan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kato%2C+Minoru%22">Kato, Minoru</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kawahara%2C+Takashi%22">Kawahara, Takashi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Goeman%2C+Lieven%22">Goeman, Lieven</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Puente%2C+Javier%22">Puente, Javier</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hellmis%2C+Eva%22">Hellmis, Eva</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Powles%2C+Thomas%22">Powles, Thomas</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Radziszewski%2C+Piotr%22">Radziszewski, Piotr</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gust%2C+Kilian+M%22">Gust, Kilian M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vasey%2C+Paul%22">Vasey, Paul</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bigot%2C+Pierre%22">Bigot, Pierre</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fradet%2C+Yves%22">Fradet, Yves</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hunting%2C+Jarmo%22">Hunting, Jarmo</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. Nov2025, Vol. 406 Issue 10516, p2221-2234. 14p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Non-muscle+invasive+bladder+cancer%22">Non-muscle invasive bladder cancer</searchLink><br /><searchLink fieldCode="DE" term="%22BCG+immunotherapy%22">BCG immunotherapy</searchLink><br /><searchLink fieldCode="DE" term="%22Treatment+effectiveness%22">Treatment effectiveness</searchLink><br /><searchLink fieldCode="DE" term="%22Adverse+health+care+events%22">Adverse health care events</searchLink><br /><searchLink fieldCode="DE" term="%22Progression-free+survival%22">Progression-free survival</searchLink><br /><searchLink fieldCode="DE" term="%22Immune+checkpoint+inhibitors%22">Immune checkpoint inhibitors</searchLink><br /><searchLink fieldCode="DE" term="%22Clinical+trials%22">Clinical trials</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) often have recurrence or progression after transurethral resection of bladder tumour (TURBT) and subsequent BCG therapy. We aimed to evaluate whether 1 year of durvalumab with BCG could improve outcomes versus BCG alone for these patients. This randomised, open-label, phase 3 trial enrolled patients aged 18 years or older with BCG-naive, high-risk NMIBC who underwent TURBT. Patients were randomly allocated (1:1:1) to receive intravenous durvalumab (every 4 weeks for 13 cycles) plus intravesical BCG induction (weekly for 6 weeks) and maintenance (three doses at weekly intervals at 3, 6, 12, 18, and 24 months), durvalumab plus BCG induction, or BCG induction and maintenance (comparison group). The primary endpoint was investigator-assessed disease-free survival in the durvalumab plus BCG induction and maintenance group versus the comparison group in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT03528694) and EudraCT (2017-002979-26) and is ongoing but is no longer enrolling patients. Between June 18, 2018, and Oct 2, 2020, 1350 patients were assessed for eligibility, among whom 1018 patients were randomly allocated: 339 to the durvalumab plus BCG induction and maintenance group (of whom 336 [99%] initiated and 180 [53%] completed treatment), 339 to the durvalumab plus BCG induction group (337 [99%] initiated and 239 [71%] completed treatment), and 340 to the comparison group (339 [>99%] initiated and 182 [54%] completed treatment). At a median follow-up of 60·7 months (IQR 51·5–66·5), there were 67 (20%) disease-free survival events in the durvalumab plus BCG induction and maintenance group and 98 (29%) events in the comparison group, resulting in a 32% reduction in the risk of recurrence of high-risk disease or death by any cause with durvalumab plus BCG induction and maintenance versus the comparison group (hazard ratio 0·68 [95% CI 0·50–0·93]; log-rank p=0·015). Among patients who received at least one dose of study treatment, grade 3 or 4 treatment-related adverse events occurred in 71 (21%) of 336 patients in the durvalumab plus BCG induction and maintenance group, 52 (15%) in the durvalumab plus BCG induction only group, and 13 (4%) of 339 patients in the comparison group. No treatment-related adverse events led to death. Among patients with BCG-naive, high-risk NMIBC, 1 year of durvalumab combined with BCG induction and maintenance therapy showed a statistically significant and clinically meaningful improvement in disease-free survival versus BCG induction and maintenance alone. The combination had a manageable safety profile, consistent with that of the individual therapies. These results support 1 year of durvalumab in combination with BCG induction and maintenance therapy as a potential new treatment for this patient population. AstraZeneca. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=189149239 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/S0140-6736(25)01897-5 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 14 StartPage: 2221 Subjects: – SubjectFull: Non-muscle invasive bladder cancer Type: general – SubjectFull: BCG immunotherapy Type: general – SubjectFull: Treatment effectiveness Type: general – SubjectFull: Adverse health care events Type: general – SubjectFull: Progression-free survival Type: general – SubjectFull: Immune checkpoint inhibitors Type: general – SubjectFull: Clinical trials Type: general Titles: – TitleFull: Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: De Santis, Maria – PersonEntity: Name: NameFull: Palou Redorta, Joan – PersonEntity: Name: NameFull: Nishiyama, Hiroyuki – PersonEntity: Name: NameFull: Krawczyński, Michał – PersonEntity: Name: NameFull: Seyitkuliev, Artur – PersonEntity: Name: NameFull: Novikov, Andrey – PersonEntity: Name: NameFull: Guerrero-Ramos, Félix – PersonEntity: Name: NameFull: Zukov, Ruslan – PersonEntity: Name: NameFull: Kato, Minoru – PersonEntity: Name: NameFull: Kawahara, Takashi – PersonEntity: Name: NameFull: Goeman, Lieven – PersonEntity: Name: NameFull: Puente, Javier – PersonEntity: Name: NameFull: Hellmis, Eva – PersonEntity: Name: NameFull: Powles, Thomas – PersonEntity: Name: NameFull: Radziszewski, Piotr – PersonEntity: Name: NameFull: Gust, Kilian M – PersonEntity: Name: NameFull: Vasey, Paul – PersonEntity: Name: NameFull: Bigot, Pierre – PersonEntity: Name: NameFull: Fradet, Yves – PersonEntity: Name: NameFull: Hunting, Jarmo IsPartOfRelationships: – BibEntity: Dates: – D: 08 M: 11 Text: Nov2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 01406736 Numbering: – Type: volume Value: 406 – Type: issue Value: 10516 Titles: – TitleFull: Lancet Type: main |
| ResultId | 1 |
