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Erschienen in: Targeted Oncology 3/2018

06.04.2018 | Original Research Article

Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies

verfasst von: Pedro C. Barata, Dhrmesh Gopalakrishnan, Vadim S. Koshkin, Prateek Mendiratta, Matt Karafa, Kimberly Allman, Allison Martin, Jennifer Beach, Pam Profusek, Allison Tyler, Laura Wood, Moshe Ornstein, Timothy Gilligan, Brian I. Rini, Jorge A. Garcia, Petros Grivas

Erschienen in: Targeted Oncology | Ausgabe 3/2018

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Abstract

Background

Little is known about the outcomes, safety, and response to subsequent therapies of patients with metastatic urothelial carcinoma (mUC) treated with atezolizumab outside clinical trials.

Objectives

The objectives of the study include to report the clinical efficacy and safety of atezolizumab, and the response to future therapies in clinical practice outside clinical trials.

Patient and Methods

This is a retrospective, single-center study including consecutive patients with confirmed mUC who received at least one dose of atezolizumab 1200 mg every 3 weeks between May 2016 and April 2017.

Results

Seventy-nine patients, median age 72 years (range 29–93), 71% men and 76% ECOG PS 0–1, were identified. Most patients (79%) had primary cancer in the bladder, 62% had prior surgery, and 75% received at least one prior line of treatment (34 patients had prior cisplatin-based chemotherapy). Best response included 18% partial response, 29% stable disease, and 53% progressive disease. Patients were on atezolizumab for a median of 2.7 months (95%CI, 1.8–3.6) and median PFS was 3.2 months (95%CI, 1.6–4.8). A total of 33 (42%) patients had significant (any cause) AEs, including grade 4 hyperbilirubinemia in two patients; no toxic deaths were reported. At time of data analysis, only 18% of patients received at least one subsequent line of treatment for a median of 1.8 months (95%CI, 0.0–5.0) while 42% were referred to palliative care/hospice or died.

Conclusions

Patients with mUC who progressed on atezolizumab were unlikely to receive subsequent systemic treatments and the benefit of those treatments appeared limited in our cohort. The findings may impact timing and designs of clinical trials in mUC.
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Literatur
3.
Zurück zum Zitat Sternberg CN, de Mulder PH, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol. 2001;19(10):2638–46. https://doi.org/10.1200/jco.2001.19.10.2638. Sternberg CN, de Mulder PH, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol. 2001;19(10):2638–46. https://​doi.​org/​10.​1200/​jco.​2001.​19.​10.​2638.
4.
Zurück zum Zitat Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Canc. 2006;42(1):50–4. https://doi.org/10.1016/j.ejca.2005.08.032. Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Canc. 2006;42(1):50–4. https://​doi.​org/​10.​1016/​j.​ejca.​2005.​08.​032.
5.
Zurück zum Zitat Loehrer PJ Sr, Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992;10(7):1066–73. https://doi.org/10.1200/jco.1992.10.7.1066. Loehrer PJ Sr, Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992;10(7):1066–73. https://​doi.​org/​10.​1200/​jco.​1992.​10.​7.​1066.
6.
Zurück zum Zitat De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012;30(2):191–9. https://doi.org/10.1200/jco.2011.37.3571. De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012;30(2):191–9. https://​doi.​org/​10.​1200/​jco.​2011.​37.​3571.
7.
Zurück zum Zitat Bellmunt J, Theodore C, Demkov T, Komyakov B, Sengelov L, Daugaard G, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009;27(27):4454–61. https://doi.org/10.1200/jco.2008.20.5534. Bellmunt J, Theodore C, Demkov T, Komyakov B, Sengelov L, Daugaard G, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009;27(27):4454–61. https://​doi.​org/​10.​1200/​jco.​2008.​20.​5534.
9.
Zurück zum Zitat Papamichael D, Gallagher CJ, Oliver RT, Johnson PW, Waxman J. Phase II study of paclitaxel in pretreated patients with locally advanced/metastatic cancer of the bladder and ureter. Br J Cancer. 1997;75(4):606–7.CrossRefPubMedPubMedCentral Papamichael D, Gallagher CJ, Oliver RT, Johnson PW, Waxman J. Phase II study of paclitaxel in pretreated patients with locally advanced/metastatic cancer of the bladder and ureter. Br J Cancer. 1997;75(4):606–7.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Albers P, Siener R, Hartlein M, Fallahi M, Haeutle D, Perabo FG, et al. Gemcitabine monotherapy as second-line treatment in cisplatin-refractory transitional cell carcinoma - prognostic factors for response and improvement of quality of life. Onkologie. 2002;25(1):47–52. doi:55202PubMed Albers P, Siener R, Hartlein M, Fallahi M, Haeutle D, Perabo FG, et al. Gemcitabine monotherapy as second-line treatment in cisplatin-refractory transitional cell carcinoma - prognostic factors for response and improvement of quality of life. Onkologie. 2002;25(1):47–52. doi:55202PubMed
13.
Zurück zum Zitat Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al. 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. 2016;387(10031):1909–20. https://doi.org/10.1016/S0140-6736(16)00561-4. Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al. 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. 2016;387(10031):1909–20. https://​doi.​org/​10.​1016/​S0140-6736(16)00561-4.
18.
Zurück zum Zitat Powles T, O’Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, et al. Efficacy and safety of Durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. JAMA Oncol. 2017;3(9):e172411. https://doi.org/10.1001/jamaoncol.2017.2411. Powles T, O’Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, et al. Efficacy and safety of Durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. JAMA Oncol. 2017;3(9):e172411. https://​doi.​org/​10.​1001/​jamaoncol.​2017.​2411.
19.
Zurück zum Zitat Powles T, Loriot Y, Duran I, Ravaud A, Retz M, Vogelzang NJ et al. IMvigor211: a phase III randomized study examining atezolizumab vs. chemotherapy for platinum. Special Conference EACR AACR SIC; June 24–27; Florence, Italy 2017. Powles T, Loriot Y, Duran I, Ravaud A, Retz M, Vogelzang NJ et al. IMvigor211: a phase III randomized study examining atezolizumab vs. chemotherapy for platinum. Special Conference EACR AACR SIC; June 24–27; Florence, Italy 2017.
21.
Zurück zum Zitat Balar A, Bellmunt J, O’Donnell PH, Castellano D, Grivas P, Vuky J, et al. Pembrolizumab (pembro) as first-line therapy for advanced/unresectable or metastatic urothelial cancer: Preliminary results from the phase 2 KEYNOTE-052 study. Ann Oncol. 2016;27(suppl_6):LBA32_PR-LBA_PR. https://doi.org/10.1093/annonc/mdw435.25.CrossRef Balar A, Bellmunt J, O’Donnell PH, Castellano D, Grivas P, Vuky J, et al. Pembrolizumab (pembro) as first-line therapy for advanced/unresectable or metastatic urothelial cancer: Preliminary results from the phase 2 KEYNOTE-052 study. Ann Oncol. 2016;27(suppl_6):LBA32_PR-LBA_PR. https://​doi.​org/​10.​1093/​annonc/​mdw435.​25.CrossRef
22.
Zurück zum Zitat Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67–76. https://doi.org/10.1016/s0140-6736(16)32455-2. Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67–76. https://​doi.​org/​10.​1016/​s0140-6736(16)32455-2.
24.
Zurück zum Zitat Bellmunt J, Albanell J, Paz-Ares L, Climent MA, González-Larriba JL, Carles J, et al. Pretreatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine. Cancer. 2002;95(4):751–7. https://doi.org/10.1002/cncr.10762.CrossRefPubMed Bellmunt J, Albanell J, Paz-Ares L, Climent MA, González-Larriba JL, Carles J, et al. Pretreatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine. Cancer. 2002;95(4):751–7. https://​doi.​org/​10.​1002/​cncr.​10762.CrossRefPubMed
26.
27.
28.
Zurück zum Zitat Necchi A, Joseph R, Loriot Y, Hoffman-Censits J, Perez-Gracia J, Petrylak D, et al. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study. Ann Oncol. 2017;28(12): 3044–50. Necchi A, Joseph R, Loriot Y, Hoffman-Censits J, Perez-Gracia J, Petrylak D, et al. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study. Ann Oncol. 2017;28(12): 3044–50.
34.
Zurück zum Zitat Anantharaman A, Friedlander T, Lu D, Krupa R, Premasekharan G, Hough J, et al. Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) in muscle invasive and metastatic bladder cancer patients. BMC Cancer. 2016;16. https://doi.org/10.1186/s12885-016-2758-3. Anantharaman A, Friedlander T, Lu D, Krupa R, Premasekharan G, Hough J, et al. Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) in muscle invasive and metastatic bladder cancer patients. BMC Cancer. 2016;16. https://​doi.​org/​10.​1186/​s12885-016-2758-3.
35.
37.
Metadaten
Titel
Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies
verfasst von
Pedro C. Barata
Dhrmesh Gopalakrishnan
Vadim S. Koshkin
Prateek Mendiratta
Matt Karafa
Kimberly Allman
Allison Martin
Jennifer Beach
Pam Profusek
Allison Tyler
Laura Wood
Moshe Ornstein
Timothy Gilligan
Brian I. Rini
Jorge A. Garcia
Petros Grivas
Publikationsdatum
06.04.2018
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 3/2018
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-018-0561-6

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