Avelumab in First Line Maintenance in Advanced Urothelial Carcinoma (aUC) in Elderly Patients: Efficacy, Tolerability, and Quality of Life in Real Life Setting
Abstract
:1. Introduction
2. Results
2.1. Patient Descriptive Characteristics
2.2. Clinical Outcomes
2.3. Quality of Life Value
2.4. Tolerability
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Patient Selection
4.3. Method of Administration
4.4. Evaluation of Response and Toxicity
4.5. Quality of Life
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Boll, L.M.; Perera-Bel, J.; Rodriguez-Vida, A.; Arpí, O.; Rovira, A.; Juanpere, N.; de Oca, S.V.M.; Hernández-Llodrà, S.; Lloreta, J.; Albà, M.M.; et al. The impact of mutational clonality in predicting the response to immune checkpoint inhibitors in advanced urothelial cancer. Sci. Rep. 2023, 13, 1–14. [Google Scholar] [CrossRef] [PubMed]
- Rosenberg, J.E.; Carroll, P.R.; Small, E.J. Update on chemotherapy for advanced bladder cancer. J. Urol. 2005, 174, 14–20. [Google Scholar] [CrossRef] [PubMed]
- Von Der Maase, H.; Hansen, S.W.; Roberts, J.T.; Dogliotti, L.; Oliver, T.; Moore, M.J.; Bodrogi, I.; Albers, P.; Knuth, A.; Lippert, C.M.; et al. Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study. J. Clin. Oncol. 2000, 18, 3068–3077. [Google Scholar] [CrossRef] [PubMed]
- 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] [PubMed]
- Bamias, A.; Dafni, U.; Karadimou, A.; Timotheadou, E.; Aravantinos, G.; Psyrri, A.; Xanthakis, I.; Tsiatas, M.; Koutoulidis, V.; Constantinidis, C.; et al. Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: A Hellenic Cooperative Oncology Group study (HE 16/03). Ann. Oncol. 2012, 24, 1011–1017. [Google Scholar] [CrossRef] [PubMed]
- Grivas, P.; Park, S.H.; Voog, E.; Caserta, C.; Gurney, H.; Bellmunt, J.; Kalofonos, H.; Ullén, A.; Loriot, Y.; Sridhar, S.S.; et al. Avelumab First-line Maintenance Therapy for Advanced Urothelial Carcinoma: Comprehensive Clinical Subgroup Analyses from the JAVELIN Bladder 100 Phase 3 Trial. Eur. Urol. 2023, 84, 95–108. [Google Scholar] [CrossRef] [PubMed]
- Powles, T.; Park, S.H.; Voog, E.; Caserta, C.; Valderrama, B.P.; Gurney, H.; Kalofonos, H.; Radulović, S.; Demey, W.; Ullén, A.; et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N. Engl. J. Med. 2020, 383, 1218–1230. [Google Scholar] [CrossRef] [PubMed]
- Canouï-Poitrine, F.; Lièvre, A.; Dayde, F.; Lopez-Trabada-Ataz, D.; Baumgaertner, I.; Dubreuil, O.; Brunetti, F.; Coriat, R.; Maley, K.; Pernot, S.; et al. Inclusion of Older Patients with Cancer in Clinical Trials: The SAGE Prospective Multicenter Cohort Survey. Oncologist 2019, 24, e1351–e1359. [Google Scholar] [CrossRef] [PubMed]
- Shao, I.H.; Lin, Y.H.; Hou, C.P.; Juang, H.H.; Chen, C.L.; Chang, P.L. Tsui KH Risk factors associated with ineligibility of adjuvant cisplatin-based chemotherapy after nephroureterectomy. Drug Des. Dev. Ther. 2014, 8, 1985–1991. [Google Scholar]
- Azam, F.; Latif, M.F.; Farooq, A.; Tirmazy, S.H.; AlShahrani, S.; Bashir, S.; Bukhari, N. Performance Status Assessment by Using ECOG (Eastern Cooperative Oncology Group) Score for Cancer Pa-tients by Oncology Healthcare Professionals. Case Rep. Oncol. 2019, 12, 728–736. [Google Scholar] [CrossRef] [PubMed]
- Alouini, S. Risk Factors Associated with Urothelial Bladder Cancer. Int. J. Environ. Res. Public Health 2024, 21, 954. [Google Scholar] [CrossRef] [PubMed]
- Jodon, G.; Fischer, S.M.; Kessler, E.R. Treatment of Urothelial Cancer in Elderly Patients: Focus on Immune Checkpoint Inhibitors. Drugs Aging 2018, 35, 409–421. [Google Scholar] [CrossRef] [PubMed]
- Ko, A.H.; Hwang, J.; Venook, A.P.; Abbruzzese, J.L.; Bergsland, E.K.; A Tempero, M. Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer. Br. J. Cancer 2005, 93, 195–199. [Google Scholar] [CrossRef] [PubMed]
- Schwartz, L.H.; Litière, S.; de Vries, E.; Ford, R.; Gwyther, S.; Mandrekar, S.; Shankar, L.; Bogaerts, J.; Chen, A.; Dancey, J.; et al. RECIST 1.1-Update and clarification: From the RECIST committee. Eur. J. Cancer. 2016, 62, 132–137. [Google Scholar] [CrossRef] [PubMed]
- Grivas, P.; Agarwal, N.; Pal, S.; Kalebasty, A.R.; Sridhar, S.S.; Smith, J.; Devgan, G.; Sternberg, C.N.; Bellmunt, J. Avelumab first-line maintenance in locally advanced or metastatic urothelial carcinoma: Applying clinical trial findings to clinical practice. Cancer Treat. Rev. 2021, 97, 102187. [Google Scholar] [CrossRef] [PubMed]
- Miller, T.P.; Fisher, B.T.; Getz, K.D.; Sack, L.; Razzaghi, H.; Seif, A.E.; Bagatell, R.; Adamson, P.C.; Aplenc, R. Unintended consequences of evolution of the Common Terminology Criteria for Adverse Events. Pediatr. Blood Cancer 2019, 66, e27747. [Google Scholar] [CrossRef] [PubMed]
- Aaronson, N.K.; Ahmedzai, S.; Bergman, B.; Bullinger, M.; Cull, A.; Duez, N.J.; Filiberti, A.; Flechtner, H.; Fleishman, S.B.; de Haes, J.C.; et al. The European Organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in interna-tional clinical trials in oncology. J. Natl. Cancer Inst. 1993, 85, 365–376. [Google Scholar] [CrossRef] [PubMed]
- Hinojosa-Gonzalez, D.E.; Saffati, G.; Salgado-Garza, G.; Patel, S.; Kronstedt, S.; Jones, J.A.; Taylor, J.M.; Yen, A.E. Slawin Novel therapeutic regimens in previously untreated metastatic urothelial carcinoma: A 13systematic review and bayesian network me-ta-analysis. JR. Urol. Oncol. 2024, S1078-1439(24)00544-1. [Google Scholar]
- Lec, P.M.; Venkataramana, A.; Lenis, A.T.; Fero, K.E.; Sharma, V.; Golla, V.; Gollapudi, K.; Blumberg, J.; Chamie, K. Trends in management of ureteral urothelial carcinoma and effects on survival: A hospital-based registry study. Urol. Oncol. Semin. Orig. Investig. 2021, 39, 194.e17–194.e24. [Google Scholar] [CrossRef] [PubMed]
- Iacovelli, R.; Cicala, C.M.; Ciccarese, C.; Sacco, E.; Racioppi, M.; Bassi, P.F.; Tortora, G. Management of metastatic urothelial carcinoma: Current approach, emerging agents, and future perspectives. Urol. J. 2022, 90, 3–10. [Google Scholar] [CrossRef] [PubMed]
n = 60 (%) | p Value | |
---|---|---|
Mean age [range] | 76 [70–88] | 0.53 |
Sex | ||
Male | 32 (53) | 0.43 |
Female | 28 (47) | 0.05 |
ECOG 1 Performance Status | ||
0 | 43 (72) | 0.12 |
1 | 17 (28) | 0.86 |
2 | - | - |
Site of tumor | ||
Bladder | 51 (85) | 1.07 |
Urethra | 9 (15) | 0.89 |
PD-L1 2 Status | ||
Positive | 32 (53) | 0.45 |
Negative | 28 (47) | 0.98 |
Location of metastasis | ||
Liver | 7 (12) | 1.48 |
Lung | 8 (14) | 0.43 |
Lymph nodes | 37 (62) | 0.46 |
Peritoneum | 14 (23) | 1.04 |
Skeletal | 7 (12) | 0.85 |
Pretreatment | ||
Cisplatin plus Gemcitabine | 16 (27) | 0.02 |
Carboplatin plus Gemcitabine | 44 (73) | 0.65 |
n = 60 (%) | p Value | |
---|---|---|
Complete response | - | - |
Partial response | 16 (27) | 1.02 |
Stable response | 38 (63) | 0.14 |
Progressive response | 6 (10) | 0.01 |
Overall Response Rate (CR 1 + PR 2) | 16(27) | 0.91 |
Disease Control Rate (CR + PR + SD 3) | 54 (90) | 1.04 |
Mean | SD | t | p | |
---|---|---|---|---|
Ca19.9 Ante-treatment | 126 | 9.04 | ||
4.68 | 0.07 | |||
Ca19.9 Post-treatment | 38 | 5.62 |
Baseline | Follow-Up | p | |
---|---|---|---|
Global health status | 56.4 | 69.8 | 0.46 |
Physical | 42.9 | 45.8 | 1.34 |
Role | 53.5 | 54.1 | 0.34 |
Cognitive | 43.3 | 44.5 | 0.01 |
Emotional | 49.8 | 48.2 | 1.53 |
Social | 41.7 | 42.1 | 0.48 |
Fatigue | 32.6 | 35.8 | 0.86 |
Pain | 48.6 | 36.2 | 1.57 |
Nausea and vomiting | 21.6 | 21.8 | 0.27 |
Dyspnea | 21.2 | 13.2 | 0.46 |
Loss of appetite | 20.3 | 21.2 | 0.84 |
Insomnia | 41.4 | 42.1 | 0.09 |
Constipation | 17.2 | 18.1 | 0.24 |
Diarrhea | 28.5 | 29.2 | 0.77 |
Financial impact | 54.2 | 46.4 | 1.09 |
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De Luca, R.; Vitale, P.; Pepe, A.; Spedaliere, R.; Simonato, A.; Addeo, R.; Cicero, G. Avelumab in First Line Maintenance in Advanced Urothelial Carcinoma (aUC) in Elderly Patients: Efficacy, Tolerability, and Quality of Life in Real Life Setting. Sci. Pharm. 2024, 92, 62. https://doi.org/10.3390/scipharm92040062
De Luca R, Vitale P, Pepe A, Spedaliere R, Simonato A, Addeo R, Cicero G. Avelumab in First Line Maintenance in Advanced Urothelial Carcinoma (aUC) in Elderly Patients: Efficacy, Tolerability, and Quality of Life in Real Life Setting. Scientia Pharmaceutica. 2024; 92(4):62. https://doi.org/10.3390/scipharm92040062
Chicago/Turabian StyleDe Luca, Rossella, Pasquale Vitale, Alessio Pepe, Roberta Spedaliere, Alchiede Simonato, Raffaele Addeo, and Giuseppe Cicero. 2024. "Avelumab in First Line Maintenance in Advanced Urothelial Carcinoma (aUC) in Elderly Patients: Efficacy, Tolerability, and Quality of Life in Real Life Setting" Scientia Pharmaceutica 92, no. 4: 62. https://doi.org/10.3390/scipharm92040062
APA StyleDe Luca, R., Vitale, P., Pepe, A., Spedaliere, R., Simonato, A., Addeo, R., & Cicero, G. (2024). Avelumab in First Line Maintenance in Advanced Urothelial Carcinoma (aUC) in Elderly Patients: Efficacy, Tolerability, and Quality of Life in Real Life Setting. Scientia Pharmaceutica, 92(4), 62. https://doi.org/10.3390/scipharm92040062