Toshiki Kijima1, Hina Yamamoto1, Kazutaka Saito2, Shota Kusuhara3, Soichiro Yoshida1, Minato Yokoyama1, Yoh Matsuoka1, Noboru Numao4, Yasuyuki Sakai5, Nobuaki Matsubara3, Takeshi Yuasa4, Hitoshi Masuda6, Junji Yonese4, Yukio Kageyama5, Yasuhisa Fujii1. 1. Department of Urology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. 2. Department of Urology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. kz-saito.uro@tmd.ac.jp. 3. Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 4. Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 5. Department of Urology, Saitama Cancer Center, Saitama, Japan. 6. Department of Urology, National Cancer Center Hospital East, Kashiwa, Japan.
Abstract
OBJECTIVE: To assess the prognostic and predictive ability of early C-reactive protein (CRP) kinetics, dynamic changes in CRP levels, in patients with advanced urothelial cancer treated with pembrolizumab. PATIENTS AND METHODS: We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab in second-line or later settings. Patients were divided into three early CRP kinetics groups: non-elevated (baseline CRP < 5 mg/L), responder (baseline CRP ≥ 5 mg/L and CRP decreased below baseline at least once within 30 days), and non-responder (baseline CRP ≥ 5 mg/L and CRP never decreased to baseline within 30 days). Association between early CRP kinetics and pembrolizumab efficacy including objective response rate (ORR), disease control rate (DCR), and overall survival (OS) were evaluated. RESULTS: Based on early CRP kinetics, 40, 27, and 30 patients were classified as non-elevated, responder, and non-responder, respectively. ORR and DCR were 33% and 60% in non-elevated, 30% and 48% in responder, and 17% and 40% in non-responder; without a statistically significant difference. OS was significantly different among the non-elevated, responder, and non-responder groups (p < 0.01), with 1-year survival rates of 69%, 61%, and 31%, respectively. Early CRP kinetics could discriminate the OS of patients without objective response. Non-responder was an independent predictor for OS (HR 3.65, p < 0.01), as well as liver metastasis and ECOG PS ≥ 2. CONCLUSION: Early CRP kinetics is associated with survival of advanced urothelial cancer patients treated with pembrolizumab and could be a potential biomarker for clinical benefit from immune checkpoint inhibitors.
OBJECTIVE: To assess the prognostic and predictive ability of early C-reactive protein (CRP) kinetics, dynamic changes in CRP levels, in patients with advanced urothelial cancer treated with pembrolizumab. PATIENTS AND METHODS: We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab in second-line or later settings. Patients were divided into three early CRP kinetics groups: non-elevated (baseline CRP < 5 mg/L), responder (baseline CRP ≥ 5 mg/L and CRP decreased below baseline at least once within 30 days), and non-responder (baseline CRP ≥ 5 mg/L and CRP never decreased to baseline within 30 days). Association between early CRP kinetics and pembrolizumab efficacy including objective response rate (ORR), disease control rate (DCR), and overall survival (OS) were evaluated. RESULTS: Based on early CRP kinetics, 40, 27, and 30 patients were classified as non-elevated, responder, and non-responder, respectively. ORR and DCR were 33% and 60% in non-elevated, 30% and 48% in responder, and 17% and 40% in non-responder; without a statistically significant difference. OS was significantly different among the non-elevated, responder, and non-responder groups (p < 0.01), with 1-year survival rates of 69%, 61%, and 31%, respectively. Early CRP kinetics could discriminate the OS of patients without objective response. Non-responder was an independent predictor for OS (HR 3.65, p < 0.01), as well as liver metastasis and ECOG PS ≥ 2. CONCLUSION: Early CRP kinetics is associated with survival of advanced urothelial cancerpatients treated with pembrolizumab and could be a potential biomarker for clinical benefit from immune checkpoint inhibitors.
Entities:
Keywords:
Biomarker; C-reactive protein kinetics; Immune checkpoint inhibitors; Overall survival; Urothelial cancer
Authors: Joaquim Bellmunt; Ronald de Wit; David J Vaughn; Yves Fradet; Jae-Lyun Lee; Lawrence Fong; Nicholas J Vogelzang; Miguel A Climent; Daniel P Petrylak; Toni K Choueiri; Andrea Necchi; Winald Gerritsen; Howard Gurney; David I Quinn; Stéphane Culine; Cora N Sternberg; Yabing Mai; Christian H Poehlein; Rodolfo F Perini; Dean F Bajorin Journal: N Engl J Med Date: 2017-02-17 Impact factor: 91.245
Authors: Lesley Seymour; Jan Bogaerts; Andrea Perrone; Robert Ford; Lawrence H Schwartz; Sumithra Mandrekar; Nancy U Lin; Saskia Litière; Janet Dancey; Alice Chen; F Stephen Hodi; Patrick Therasse; Otto S Hoekstra; Lalitha K Shankar; Jedd D Wolchok; Marcus Ballinger; Caroline Caramella; Elisabeth G E de Vries Journal: Lancet Oncol Date: 2017-03-02 Impact factor: 41.316
Authors: Bernard A Fox; Dolores J Schendel; Lisa H Butterfield; Steinar Aamdal; James P Allison; Paolo Antonio Ascierto; Michael B Atkins; Jirina Bartunkova; Lothar Bergmann; Neil Berinstein; Cristina C Bonorino; Ernest Borden; Jonathan L Bramson; Cedrik M Britten; Xuetao Cao; William E Carson; Alfred E Chang; Dainius Characiejus; A Raja Choudhury; George Coukos; Tanja de Gruijl; Robert O Dillman; Harry Dolstra; Glenn Dranoff; Lindy G Durrant; James H Finke; Jerome Galon; Jared A Gollob; Cécile Gouttefangeas; Fabio Grizzi; Michele Guida; Leif Håkansson; Kristen Hege; Ronald B Herberman; F Stephen Hodi; Axel Hoos; Christoph Huber; Patrick Hwu; Kohzoh Imai; Elizabeth M Jaffee; Sylvia Janetzki; Carl H June; Pawel Kalinski; Howard L Kaufman; Koji Kawakami; Yutaka Kawakami; Ulrich Keilholtz; Samir N Khleif; Rolf Kiessling; Beatrix Kotlan; Guido Kroemer; Rejean Lapointe; Hyam I Levitsky; Michael T Lotze; Cristina Maccalli; Michele Maio; Jens-Peter Marschner; Michael J Mastrangelo; Giuseppe Masucci; Ignacio Melero; Cornelius Melief; William J Murphy; Brad Nelson; Andrea Nicolini; Michael I Nishimura; Kunle Odunsi; Pamela S Ohashi; Jill O'Donnell-Tormey; Lloyd J Old; Christian Ottensmeier; Michael Papamichail; Giorgio Parmiani; Graham Pawelec; Enrico Proietti; Shukui Qin; Robert Rees; Antoni Ribas; Ruggero Ridolfi; Gerd Ritter; Licia Rivoltini; Pedro J Romero; Mohamed L Salem; Rik J Scheper; Barbara Seliger; Padmanee Sharma; Hiroshi Shiku; Harpreet Singh-Jasuja; Wenru Song; Per Thor Straten; Hideaki Tahara; Zhigang Tian; Sjoerd H van Der Burg; Paul von Hoegen; Ena Wang; Marij Jp Welters; Hauke Winter; Tara Withington; Jedd D Wolchok; Weihua Xiao; Laurence Zitvogel; Heinz Zwierzina; Francesco M Marincola; Thomas F Gajewski; Jon M Wigginton; Mary L Disis Journal: J Transl Med Date: 2011-12-14 Impact factor: 5.531
Authors: J Ishioka; K Saito; M Sakura; M Yokoyama; Y Matsuoka; N Numao; F Koga; H Masuda; Y Fujii; S Kawakami; K Kihara Journal: Br J Cancer Date: 2012-08-23 Impact factor: 7.640