Neoadjuvant Therapy Using Checkpoint Inhibitors before Radical Cystectomy for Muscle Invasive Bladder Cancer: A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Data Extraction
2.3. Primary Outcomes
2.4. Statistical Analysis
2.5. Risk of Bias Assessment
3. Results
3.1. Search Results
3.2. Oncological Response
3.3. Safety and Side Effects
3.4. Surgical Complications
3.5. Survival Outcomes
3.6. Subgroup Quantitative Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Martini, A.; Sfakianos, J.P.; Renström-Koskela, L.; Mortezavi, A.; Falagario, U.G.; Egevad, L.; Hosseini, A.; Mehrazin, R.; Galsky, M.D.; Steineck, G.; et al. The natural history of untreated muscle-invasive bladder cancer. BJU Int. 2020, 125, 270–275. [Google Scholar] [CrossRef] [PubMed]
- Fahmy, O.; Khairul-Asri, M.G.; Schubert, T.; Renninger, M.; Malek, R.; Kübler, H.; Stenzl, A.; Gakis, G. A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer. Urol. Oncol. 2018, 36, 43–53. [Google Scholar] [CrossRef] [PubMed]
- Morales, A.; Eidinger, D.; Bruce, A.W. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J. Urol. 1976, 116, 180–183. [Google Scholar] [CrossRef]
- Fahmy, O.; Khairul-Asri, M.G.; Stenzl, A.; Gakis, G. Systemic anti-CTLA−4 and intravesical Bacille-Calmette-Guerin therapy in non-muscle invasive bladder cancer: Is there a rationale of synergism? Med. Hypotheses 2016, 92, 57–58. [Google Scholar] [CrossRef]
- Vale, C.L. Neoadjuvant chemotherapy in invasive bladder cancer: Update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur. Urol. 2005, 48, 202. [Google Scholar] [CrossRef]
- von der Maase, H.; Sengelov, L.; Roberts, J.T.; Ricci, S.; Dogliotti, L.; Oliver, T.; Moore, M.J.; Zimmermann, A.; Arning, M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J. Clin. Oncol. 2005, 23, 4602–4608. [Google Scholar] [CrossRef]
- Yin, M.; Joshi, M.; Meijer, R.P.; Glantz, M.; Holder, S.; Harvey, H.A.; Kaag, M.; Fransen van de Putte, E.E.; Horenblas, S.; Drabick, J.J. Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Systematic Review and Two-Step Meta-Analysis. Oncologist 2016, 21, 708–715. [Google Scholar] [CrossRef] [Green Version]
- Fahmy, O.; Khairul-Asri, M.G.; Stenzl, A.; Gakis, G. The current status of checkpoint inhibitors in metastatic bladder cancer. Clin. Exp. Metast. 2016, 33, 629–635. [Google Scholar] [CrossRef]
- Roviello, G.; Catalano, M.; Santi, R.; Palmieri, V.E.; Vannini, G.; Galli, I.C.; Buttitta, E.; Villari, D.; Rossi, V.; Nesi, G. Immune Checkpoint Inhibitors in Urothelial Bladder Cancer: State of the Art and Future Perspectives. Cancers 2021, 13, 4411. [Google Scholar] [CrossRef]
- 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.; et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N. Engl. J. Med. 2021, 384, 2102–2114. [Google Scholar] [CrossRef]
- Moher, D.; Shamseer, L.; Clarke, M.; Ghersi, D.; Liberati, A.; Petticrew, M.; Shekelle, P.; Stewart, L.A. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev. 2015, 4, 1. [Google Scholar] [CrossRef] [Green Version]
- Wells, G.A.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. Ottawa Hospital Research Institute. Available online: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed on 10 September 2021).
- Powles, T.; Kockx, M.; Rodriguez-Vida, A.; Duran, I.; Crabb, S.J.; Van Der Heijden, M.S.; Szabados, B.; Pous, A.F.; Gravis, G.; Herranz, U.A. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS. Nat. Med. 2019, 25, 1706–1714. [Google Scholar] [CrossRef]
- Necchi, A.; Raggi, D.; Gallina, A.; Madison, R.; Colecchia, M.; Lucianò, R.; Montironi, R.; Giannatempo, P.; Farè, E.; Pederzoli, F.; et al. Updated Results of PURE-01 with Preliminary Activity of Neoadjuvant Pembrolizumab in Patients with Muscle-invasive Bladder Carcinoma with Variant Histologies. Eur. Urol. 2020, 77, 439–446. [Google Scholar] [CrossRef]
- Rodriguez-Moreno, J.F.; de Velasco, G.; Bravo Fernandez, I. Impact of the Combination of Durvalumab (MEDI4736) Plus Olaparib (AZD2281) Administered Prior to Surgery in the Molecular Profile of Resectable Urothelial Bladder Cancer: NEODURVARIB Trial. J. Clin. Oncol. 2020, 38, 542. [Google Scholar] [CrossRef]
- Cathomas, R.; Petrausch, U.; Hayoz, S. Perioperative chemoimmunotherapy with durvalumab (Durva) in combination with cisplatin/gemcitabine (Cis/Gem) for operable muscle-invasive urothelial carcinoma (MIUC): Preplanned interim analysis of a single-arm phase II trial (SAKK 06/17). J. Clin. Oncol. 2020, 20, 499. [Google Scholar] [CrossRef]
- Gupta, S.; Sonpavde, G.; Weight, C.J. Results from BLASST−1 (Bladder Cancer Signal Seeking Trial) of nivolumab, gemcitabine, and cisplatin in muscle invasive bladder cancer (MIBC) undergoing cystectomy. J. Clin. Oncol. 2020, 20, 439. [Google Scholar] [CrossRef]
- Hoimes, C.J.; Albany, C.; Hoffman-Censits, J. A phase Ib/II study of neoadjuvant pembrolizumab (pembro) and chemotherapy for locally advanced urothelial cancer (UC). Clin. Oncol. 2020, 38, 5047. [Google Scholar] [CrossRef]
- Van Dijk, N.; Gil-Jimenez, A.; Silina, K.; Hendricksen, K.; Smit, L.A.; de Feijter, J.M.; van Montfoort, M.L.; van Rooijen, C.; Peters, D.; Broeks, A. Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: The NABUCCO trial. Nat. Med. 2020, 26, 1839–1844. [Google Scholar] [CrossRef]
- Gao, J.; Navai, N.; Alhalabi, O.; Siefker-Radtke, A.; Campbell, M.T.; Tidwell, R.S.; Guo, C.C.; Kamat, A.M.; Matin, S.F.; Araujo, J.C. Neoadjuvant PD-L1 plus CTLA−4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nat. Med. 2020, 26, 1845–1851. [Google Scholar] [CrossRef]
- Dindo, D.; Demartines, N.; Clavien, P.A. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann. Surg. 2004, 240, 205–213. [Google Scholar] [CrossRef]
- Necchi, A.; Anichini, A.; Raggi, D.; Briganti, A.; Massa, S.; Lucianò, R.; Colecchia, M.; Giannatempo, P.; Mortarini, R.; Bianchi, M.; 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lopez-Beltran, A.; Cimadamore, A.; Blanca, A.; Massari, F.; Vau, N.; Scarpelli, M.; Cheng, L.; Montironi, R. Immune Checkpoint Inhibitors for the Treatment of Bladder Cancer. Cancers 2021, 13, 131. [Google Scholar] [CrossRef] [PubMed]
- Samstein, R.M.; Lee, C.H.; Shoushtari, A.N.; Hellmann, M.D.; Shen, R.; Janjigian, Y.Y.; Barron, D.A.; Zehir, A.; Jordan, E.J.; Omuro, A. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat. Genet. 2019, 51, 202–206. [Google Scholar] [CrossRef] [PubMed]
- Davarpanah, N.N.; Yuno, A.; Trepel, J.B.; Apolo, A.B. Immunotherapy: A new treatment paradigm in bladdercancer. Curr. Opin. Oncol. 2017, 29, 184–195. [Google Scholar] [CrossRef] [Green Version]
- Raphael, M.J.; Booth, C.M. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: Underused across the 49th parallel. Can. Urol. Assoc. J. 2019, 13, 29–31. [Google Scholar] [CrossRef]
- Silva, A.L.; Abreu-Mendes, P.; Martins, D.; Mendes, F. The Impact of Immune Checkpoint-Inhibitors Therapy in Urinary Bladder Cancer. Onco 2021, 1, 3–22. [Google Scholar] [CrossRef]
Study | Country | Trial Name | Type | Neoadjuvant Treatment | No. of Patients | Male/Female | Mean Age |
---|---|---|---|---|---|---|---|
Powles 2019 [13] | UK | ABACUS | single-arm phase II | Atezolizumab | 95 | 81/14 | 73 |
Necchi 2020 [14] | Italy | PURE−01 | single-arm phase II | Pembrolizumab | 114 | 99/15 | 66 |
Moreno 2020 [15] | Spain | NEODURVARIB | single-arm phase II | Durvalumab + Chemo | 29 | 26/3 | 71 |
Cathomas 2020 [16] | Switzerland | SAKK−06/17 | single-arm phase II | Durvalumab + Chemo | 34 | 27/7 | 70 |
Gupta 2020 [17] | USA | BLASST−1 | single-arm phase II | Nivolumab + Chemo | 41 | - | - |
Hoimes 2020 [18] | USA | - | 3-arm Phase Ib/II | Pembrolizumab + Chemo | 40 | 30/10 | 65 |
Dijk 2020 [19] | Netherland | NABUCCO | single-arm phase I | Nivolumab + Ipilimumab | 24 | 18/6 | 65(50–81) |
Gao 2020 [20] | USA | - | single-arm phase I | Durvalumab + Termelimumab | 27 * | 20/8 | 71(24–83) |
Study | Selection | Comparability | Outcome | Overall | |||||
---|---|---|---|---|---|---|---|---|---|
Representativeness of Exposed Cohort | Selection of Nonexposed | Ascertainment of Exposure | Outcome not Present at Start | Assessment of Outcome | Adequate Follow-up Length | Adequacy of Follow-up | |||
Powles 2019 [13] | * | * | * | * | * | * | 6/9 | ||
Necchi 2020 [14] | * | * | * | * | * | * | 6/9 | ||
Moreno 2020 [15] | * | * | * | * | * | 5/9 | |||
Cathomas 2020 [16] | * | * | * | * | * | 5/9 | |||
Gupta 2020 [17] | * | * | * | * | * | 5/9 | |||
Hoimes 2020 [18] | * | * | * | * | * | 5/9 | |||
Dijk 2020 [19] | * | * | * | * | * | * | 6/9 | ||
Gao 2020 [20] | * | * | * | * | * | * | 6/9 |
Study | DS | CR | AE (%) | RC (%) | Surgical Complications (%) | 1 y OS | 1 y RFS | ||
---|---|---|---|---|---|---|---|---|---|
All Grades | ≥ Grade 3 | All Grades | ≥ Grade 3 | ||||||
Powles 2019 [13] | - | 31% | 49/95 (52) | 10/95 (11) | 87/95 (92) | 54/87 (62) | 15/87 (17) | - | 79% |
Necchi 2020 [14] | 55% | 37% | 85/114 (75) | 8/114 (7) | 112/114 (98) | 69/112 (62) | 26/112 (23) | - | - |
Moreno 2020 [15] | 74% | 50% | NA | 1/29 (3) | 26/29 (90) | NA | 5/20 (25) | - | - |
Cathomas 2020 [16] | 50% | 30% | NA | 8/34 (24) | 30/34 (88) | 13/30 (43) | 8/30 (27) | - | - |
Gupta 2020 [17] | 66% | - | NA | 8/41 (20) | 40/41 (98) | NA | NA | - | - |
Hoimes 2020 [18] | 55% | 44% | NA | NA | 36/40 (90) | NA | NA | 94% | 80% |
Dijk 2020 [19] | 58% | 46% | NA | 13/24 (55) | 24/24 (100) | NA | NA | 92% | 88% |
Gao 2020 [20] | 58% | 37% | 25/27 (93) | 6/27 (21) | 23/27 (86) | 5/23 (22) | NA | 88% | 82% |
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SHSM, H.; Fahmy, U.A.; Alhakamy, N.A.; Khairul-Asri, M.G.; Fahmy, O. Neoadjuvant Therapy Using Checkpoint Inhibitors before Radical Cystectomy for Muscle Invasive Bladder Cancer: A Systematic Review. J. Pers. Med. 2021, 11, 1195. https://doi.org/10.3390/jpm11111195
SHSM H, Fahmy UA, Alhakamy NA, Khairul-Asri MG, Fahmy O. Neoadjuvant Therapy Using Checkpoint Inhibitors before Radical Cystectomy for Muscle Invasive Bladder Cancer: A Systematic Review. Journal of Personalized Medicine. 2021; 11(11):1195. https://doi.org/10.3390/jpm11111195
Chicago/Turabian StyleSHSM, Hadi, Usama A. Fahmy, Nabil A. Alhakamy, Mohd G. Khairul-Asri, and Omar Fahmy. 2021. "Neoadjuvant Therapy Using Checkpoint Inhibitors before Radical Cystectomy for Muscle Invasive Bladder Cancer: A Systematic Review" Journal of Personalized Medicine 11, no. 11: 1195. https://doi.org/10.3390/jpm11111195