Atezolizumab in Patients with Pretreated Urothelial Cancer: A Korean Single-Center, Retrospective Study
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Purpose Treatment targeting immune checkpoint with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has demonstrated efficacy and tolerability in the treatment of metastatic urothelial carcinoma (mUC). We investigated the efficacy and safety of atezolizumab in mUC patients who failed platinum-based chemotherapy. Materials and Methods A retrospective study using the Samsung Medical Center cancer chemotherapy registry was performed on 50 consecutive patients with mUC treated with atezolizumab, regardless of their PD-L1 (SP142) status, as salvage therapy after chemotherapy failure between May 2017 and June 2018. Endpoints included overall response rate (RR), progression-free survival (PFS), and safety. Results Among 50 patients, men constituted 76% and the median age was 68 years (range, 46 to 82 years). Twenty-three patients (46%) received atezolizumab as second-line therapy. PD-L1 (SP142) status IC0/1 and IC2/3 were found in 21 (42%) and 21 (42%) of patients, respectively; in eight patients (16%), PD-L1 (SP142) expression was not available. Atezolizumab was generally well tolerated, with pruritus and fatigue being the most commonly observed toxicities. As a result, partial response was noted in 20 patients (40%), with 12 (24%) stable diseases. RR was higher in IC2/3 (62%) than in IC0/1 patients (24%, p=0.013). The median PFS was 7.4 months (95% confidence interval, 3.4 to 11.4 months). As expected, PFS also was significantly longer in IC2/3 patients than in IC0/1 (median, 12.7 vs. 2.1 months; p=0.005). PFS was not significantly influenced by age, sex, performance status, number of previous chemotherapy, site of metastases, or any of the baseline laboratory parameters. Conclusion In this retrospective study, atezolizumab demonstrated clinically efficacy and tolerability in unselected mUC patients who failed platinum-based chemotherapy.
Abstract
Purpose Treatment targeting immune checkpoint with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has demonstrated efficacy and tolerability in the treatment of metastatic urothelial carcinoma (mUC). We investigated the efficacy and safety of atezolizumab in mUC patients who failed platinum-based chemotherapy. Materials and Methods A retrospective study using the Samsung Medical Center cancer chemotherapy registry was performed on 50 consecutive patients with mUC treated with atezolizumab, regardless of their PD-L1 (SP142) status, as salvage therapy after chemotherapy failure between May 2017 and June 2018. Endpoints included overall response rate (RR), progression-free survival (PFS), and safety. Results Among 50 patients, men constituted 76% and the median age was 68 years (range, 46 to 82 years). Twenty-three patients (46%) received atezolizumab as second-line therapy. PD-L1 (SP142) status IC0/1 and IC2/3 were found in 21 (42%) and 21 (42%) of patients, respectively; in eight patients (16%), PD-L1 (SP142) expression was not available. Atezolizumab was generally well tolerated, with pruritus and fatigue being the most commonly observed toxicities. As a result, partial response was noted in 20 patients (40%), with 12 (24%) stable diseases. RR was higher in IC2/3 (62%) than in IC0/1 patients (24%, p=0.013). The median PFS was 7.4 months (95% confidence interval, 3.4 to 11.4 months). As expected, PFS also was significantly longer in IC2/3 patients than in IC0/1 (median, 12.7 vs. 2.1 months; p=0.005). PFS was not significantly influenced by age, sex, performance status, number of previous chemotherapy, site of metastases, or any of the baseline laboratory parameters. Conclusion In this retrospective study, atezolizumab demonstrated clinically efficacy and tolerability in unselected mUC patients who failed platinum-based chemotherapy.
참고문헌 (14)
- Roscigno M, "Assessment of the minimum number of lymph nodes needed to detect lymph node invasion at radical nephroureterectomy in patients with upper tract urothelial cancer", Urology, 74, pp.1070~1074 (2009)
- Siegel R, "Cancer statistics, 2014", CA Cancer J Clin, 64, pp.9~29 (2014)
- von der Maase H, "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, 23, pp.4602~4608 (2005)
- Rosenberg JE, "Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy : a single-arm, multicentre, phase 2 trial", Lancet, 387, pp.1909~1920 (2016)
- Bellmunt J, "Pembrolizumab as second-line therapy for advanced urothelial carcinoma", N Engl J Med, 376, pp.1015~1026 (2017)
- Powles T, "Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma(IMvigor211) : a multicentre, open-label, phase 3 randomised controlled trial", Lancet, 391, pp.748~757 (2018)
- Sharma P, "Nivolumab in metastatic urothelial carcinoma after platinum therapy(CheckMate 275) : a multicentre, singlearm, phase 2 trial", Lancet Oncol, 18, pp.312~322 (2017)
- Powles T, "Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma:updated results from a phase 1", 2 open-label study, 2017, pp.3, e172411~
- Patel MR, "Avelumab in metastatic urothelial carcinoma after platinum failure(JAVELIN Solid Tumor) : pooled results from two expansion cohorts of an open-label, phase 1 trial", Lancet Oncol, 19, pp.51~64 (2018)
- Kim ST, "Correlating programmed death ligand 1 (PD-L1) expression, mismatch repair deficiency, and outcomes across tumor types: implications for immunotherapy", Oncotarget, 8, pp.77415~77423 (2017)
- Salem ME, "Landscape of tumor mutation load, mismatch repair deficiency, and PD-L1 expression in a large patient cohort of gastrointestinal cancers", Mol Cancer Res, 16, pp.805~812 (2018)
- Lamm DL, "Bladder cancer immunotherapy", J Urol, 128, pp.931~935 (1982)
- Balar AV, "Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma : a single-arm, multicentre, phase 2 trial", Lancet, 389, pp.67~76 (2017)
- Balar AV, "First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer(KEYNOTE-052) : a multicentre, single-arm, phase 2 study", Lancet Oncol, 18, pp.1483~1492 (2017)