Survival after neoadjuvant/induction combination immunotherapy vs combination platinum-based chemotherapy for locally advanced (Stage III) urothelial cancer.
Antineoplastic Combined Chemotherapy Protocols
Carboplatin
Carcinoma, Transitional Cell
/ drug therapy
Cisplatin
Humans
Immune Checkpoint Inhibitors
Immunotherapy
Ipilimumab
/ therapeutic use
Neoadjuvant Therapy
Nivolumab
/ therapeutic use
Platinum
/ therapeutic use
Urinary Bladder Neoplasms
/ drug therapy
checkpoint inhibition
chemotherapy
immune
neoadjuvant
urothelial cancer
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 Dec 2022
01 Dec 2022
Historique:
revised:
22
04
2022
received:
13
02
2022
accepted:
26
04
2022
pubmed:
24
5
2022
medline:
18
10
2022
entrez:
23
5
2022
Statut:
ppublish
Résumé
Despite treatment with cisplatin-based chemotherapy and surgical resection, clinical outcomes of patients with locally advanced urothelial carcinoma (UC) remain poor. We compared neoadjuvant/induction platinum-based combination chemotherapy (NAIC) with combination immune checkpoint inhibition (cICI). We identified 602 patients who attended our outpatient bladder cancer clinic in 2018 to 2019. Patients were included if they received NAIC or cICI for cT3-4aN0M0 or cT1-4aN1-3M0 UC. NAIC consisted of cisplatin-based chemotherapy or gemcitabine-carboplatin in case of cisplatin-ineligibility. A subset of patients (cisplatin-ineligibility or refusal of NAIC) received ipilimumab plus nivolumab in the NABUCCO-trial (NCT03387761). Treatments were compared using the log-rank test and propensity score-weighted Cox regression models. We included 107 Stage III UC patients treated with NAIC (n = 83) or cICI (n = 24). NAIC was discontinued in 11 patients due to progression (n = 6; 7%) or toxicity (n = 5; 6%), while cICI was discontinued in 6 patients (25%) after 2 cycles due to toxicity (P = .205). After NAIC, patients had surgical resection (n = 50; 60%), chemoradiation (n = 26; 30%), or no consolidating treatment due to progression (n = 5; 6%) or toxicity (n = 2; 2%). After cICI, all patients underwent resection. After resection (n = 74), complete pathological response (ypT0N0) was achieved in 11 (22%) NAIC-patients and 11 (46%) cICI-patients (P = .056). Median (IQR) follow-up was 26 (20-32) months. cICI was associated with superior progression-free survival (P = .003) and overall survival (P = .003) compared to NAIC. Our study showed superior survival in Stage III UC patients pretreated with cICI if compared to NAIC. Our findings provide a strong rationale for validation of cICI for locally advanced UC in a comparative phase-3 trial.
Substances chimiques
Immune Checkpoint Inhibitors
0
Ipilimumab
0
Nivolumab
31YO63LBSN
Platinum
49DFR088MY
Carboplatin
BG3F62OND5
Cisplatin
Q20Q21Q62J
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2004-2011Informations de copyright
© 2022 UICC.
Références
Nguyen DP, Thalmann GN. Contemporary update on neoadjuvant therapy for bladder cancer. Nat Rev Urol. 2017;14:348-358.
Witjes JA, Bruins HM, Cathomas R, et al. European Association of Urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines. Eur Urol. 2021;79:82-104.
Hermans TJN, Fransen Van De Putte EE, Horenblas S, et al. Pathological downstaging and survival after induction chemotherapy and radical cystectomy for clinically node-positive bladder cancer-results of a nationwide population-based study. Eur J Cancer. 2016;69:1-8.
Powles T, Kockx M, Rodriguez-Vida A, et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019;25:1706-1714.
Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): an open-label, single-arm, phase II study. J Clin Oncol. 2018;36:3353-3360.
Gao J, Navai N, Alhalabi O, et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nat Med. 2020;26:1845-1851.
van Dijk N, Gil-Jimenez A, Silina K, et al. Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial. Nat Med. 2020;26:1839-1844.
Galsky MD, Hahn NM, Rosenberg J, et al. A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol. 2011;12:211-214.
Voskuilen CS, van de Kamp MW, Schuring N, et al. Radiation with concurrent radiosensitizing capecitabine tablets and single-dose mitomycin-C for muscle-invasive bladder cancer: a convenient alternative to 5-fluorouracil. Radiother Oncol. 2020;150:275-280.
Mertens LS, Meijer RP, Meinhardt W, et al. Occult lymph node metastases in patients with carcinoma invading bladder muscle: incidence after neoadjuvant chemotherapy and cystectomy vs after cystectomy alone. BJU Int. 2014;114:67-74.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer [Internet]; 2021; https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed September 22, 2021.
Rosenblatt R, Sherif A, Rintala E, et al. Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive urothelial bladder cancer. Eur Urol. 2012;61:1229-1238.
Sonpavde G, Goldman BH, Speights VO, et al. Quality of pathologic response and surgery correlate with survival for patients with completely resected bladder cancer after neoadjuvant chemotherapy. Cancer. 2009;115:4104-4109.