First-line avelumab for patients with PD-L1-positive metastatic or locally advanced urothelial cancer who are unfit for cisplatin

被引:13
作者
Iacovelli, R. [1 ,22 ]
Ciccarese, C. [1 ]
Brunelli, M. [2 ,3 ]
Battelli, N.
Buttigliero, C. [4 ]
Caserta, C. [5 ]
Buti, S. [6 ,7 ]
Santini, D. [8 ,9 ]
Carella, C. [10 ]
Galli, L. [11 ]
Verri, E. [12 ]
Ermacora, P. [13 ]
Merler, S. [14 ]
Masini, C. [15 ]
De Vivo, R. [16 ]
Milesi, L. [17 ]
Spina, F. [18 ]
Rizzo, M. [19 ]
Sperduti, I. [20 ]
Fornarini, G. [21 ]
Tortora, G. [1 ]
机构
[1] Fdn Policlin Univ A Gemelli IRCCS, Oncol Unit, Rome, Italy
[2] Univ Verona, Dept Diagnost & Publ Hlth, Pathol Unit, Azienda Osped Unive Integrata Verona, Verona, Italy
[3] Osped Gen Prov Macerata, Oncol Med, Macerata, Italy
[4] Univ Turin, San Luigi Gonzaga Hosp, Dept Oncol, Turin, Italy
[5] Azienda Osped Santa Maria, Med & Translat Oncol Unit, Terni, Italy
[6] Univ Hosp Parma, Med Oncol Unit, Parma, Italy
[7] Univ Parma, Dept Med & Surg, Parma, Italy
[8] Campus Biomed Univ Rome, Dept Med Oncol, Rome, Italy
[9] Univ La Sapienza, UOC Oncol Med, Polo Pontino, Latina, Italy
[10] Ist tumori Giovanni Paolo II, Bari, Italy
[11] Azienda Osped Univ Pisana, Med Oncol Unit 2, Pisa, Italy
[12] European Inst Oncol, Med Oncol Div Urogenital & Head & Neck Tumors, Milan, Italy
[13] Azienda Osped Univ, Dept Oncol, Udine, Italy
[14] Univ Verona, Sch Med, Sect Oncol, Verona, Italy
[15] AUSL IRCCS Reggio Emilia, Oncol Unit, Reggio Emilia, Italy
[16] San Bortolo Gen Hosp, Azienda ULSS8 Ber, Dept Oncol, Vicenza, Italy
[17] Oncol Med Asst Papa Giovanni XXIII, Bergamo, Italy
[18] Grande Osped Metropolitano Niguarda, Niguarda Canc Ctr, Dept Hematol Oncol & Mol Med, Milan, Italy
[19] IRCCS Ist Clin Sci Maugeri, Div Translat Oncol, Pavia, Italy
[20] IRCCS Regina Elena Natl Canc Inst, Biostat Unit, Rome, Italy
[21] IRCCS Osped Policlin San Martino, UO Oncol Med 1, Genoa, Italy
[22] Fdn Policlin Univ Agostino Gemelli IRCCS, Oncol Med, Largo Agostino Gemelli 8, I-00158 Rome, Italy
关键词
avelumab; biomarkers; bladder cancer; cisplatin ineligible; immunotherapy; PD-L1; OPEN-LABEL; INELIGIBLE PATIENTS; BLADDER-CANCER; CELL-CARCINOMA; SINGLE-ARM; CHEMOTHERAPY; PEMBROLIZUMAB; MULTICENTER; KEYNOTE-052; THERAPY;
D O I
10.1016/j.annonc.2022.07.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Cisplatin-based chemotherapy is the most recommended treatment for metastatic urothelial cancer (mUC). However, about 50% of patients are considered to be cisplatin ineligible. Anti-programmed cell death protein 1/programmed death-ligand 1 (PD-L1) therapies have, nevertheless, increased the options available to clinicians and are especially valuable for treating these patients. This study therefore tested the activity and safety of avelumab as first-line therapy for mUC.Patients and methods: Patients with mUC who were ineligible for cisplatin-based chemotherapy were screened centrally for PD-L1 expression and only those with a tumour proportion score > 5% were enrolled in the trial. The primary endpoint was 1-year overall survival (OS), and the secondary endpoints were median OS, median progression-free survival, overall response rate, duration of the response, safety and tolerability. All the survival rates were estimated with the KaplaneMeier product-limit methodology and compared across groups using the log -rank test.Results: A total of 198 patients were screened, with 71 (35.9%) whose PD-L1 expression was >5% enrolled in the study. The median age was 75 years, bladder cancer was the primary tumour in 73.2% of cases and 25.3% had liver metastases. The main reasons for the cisplatin ineligibility were a low rate of creatinine clearance (<60 ml/min), present in 70.4% of patients, and an Eastern Cooperative Oncology Group performance status of 2, which affected 31%. The median OS was 10.0 months (95% confidence interval 5.5-14.5 months) and 43% of patients were alive at 1 year. A complete response was achieved in 8.5% of cases, and 15.5% had a partial response. Adverse any-grade and high-grade events occurred in 49.3% and 8.5% of patients, respectively. A grade 3 infusion reaction was the only high-grade treatment-related adverse event. No treatment-related deaths were reported.Conclusions: This ARIES trial confirmed the activity and safety of avelumab for treating mUC, adding a new therapy option to the armamentarium of checkpoint inhibitors already approved for platinum-ineligible, locally advanced/mUC.
引用
收藏
页码:1179 / 1185
页数:7
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