Bernadett Szabados1, Nick van Dijk2, Yen Zhi Tang3, Michiel S van der Heijden2, Akhila Wimalasingham3, Alfonso Gomez de Liano3, Simon Chowdhury4, Simon Hughes4, Sarah Rudman4, Mark Linch5, Thomas Powles6. 1. Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Urology, University of Munich, Klinikum Grosshadern, Germany. 2. Netherlands Cancer Institute, Amsterdam, The Netherlands. 3. Barts Cancer Institute, Queen Mary University of London, London, UK. 4. Guys and St Thomas' Hospital, London, UK. 5. University College London, London, UK. 6. Barts Cancer Institute, Queen Mary University of London, London, UK. Electronic address: Thomas.powles@bartshealth.nhs.uk.
Abstract
Immune checkpoint inhibitors (ICIs) are active in metastatic urothelial carcinoma (MUC). They have joined chemotherapy (CT) as a standard of care. Here, we investigate the activity of CT after progression on ICIs. Two cohorts of sequential patients with MUC were described (n=28). Cohort A received first-line ICIs followed by CT after progression. Cohort B received CT after failure of first-line platinum-based CT followed by ICIs. Response rate (RR) to CT was assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) by a designated radiologist. Best RR for cohort A was 64%. Two patients experienced clinical progression and died before the first radiographic assessment. RR for cohort B was 21%, which was significantly lower than that for cohort A. Progression of disease occurred in 43% of cohort B patients by the end of CT. These data suggest a lack of cross resistance between CT and ICIs in MUC. Therefore, the sequencing of these drugs is likely to be important to maximise outcomes. This is particularly true after first-line ICIs as subsequent CT has significant activity. PATIENT SUMMARY: In this report, we studied the effect of chemotherapy in metastatic bladder cancer, which relapsed after immune checkpoint inhibitors. We found that the activity of chemotherapy was maintained despite previous exposure to immune therapy. This underlines the importance of sequencing these agents to maximise outcomes.
Immune checkpoint inhibitors (ICIs) are active in metastatic urothelial carcinoma (MUC). They have joined chemotherapy (CT) as a standard of care. Here, we investigate the activity of CT after progression on ICIs. Two cohorts of sequential patients with MUC were described (n=28). Cohort A received first-line ICIs followed by CT after progression. Cohort B received CT after failure of first-line platinum-based CT followed by ICIs. Response rate (RR) to CT was assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) by a designated radiologist. Best RR for cohort A was 64%. Two patients experienced clinical progression and died before the first radiographic assessment. RR for cohort B was 21%, which was significantly lower than that for cohort A. Progression of disease occurred in 43% of cohort B patients by the end of CT. These data suggest a lack of cross resistance between CT and ICIs in MUC. Therefore, the sequencing of these drugs is likely to be important to maximise outcomes. This is particularly true after first-line ICIs as subsequent CT has significant activity. PATIENT SUMMARY: In this report, we studied the effect of chemotherapy in metastatic bladder cancer, which relapsed after immune checkpoint inhibitors. We found that the activity of chemotherapy was maintained despite previous exposure to immune therapy. This underlines the importance of sequencing these agents to maximise outcomes.
Authors: Laura-Maria Krabbe; Vitaly Margulis; Andres Jan Schrader; Shahrokh F Shariat; Kilian M Gust; Martin Boegemann Journal: World J Urol Date: 2018-06-08 Impact factor: 4.226
Authors: Georgios Kallifatidis; Diandra K Smith; Daley S Morera; Jie Gao; Martin J Hennig; James J Hoy; Richard F Pearce; Isha R Dabke; Jiemin Li; Axel S Merseburger; Markus A Kuczyk; Vinata B Lokeshwar; Bal L Lokeshwar Journal: Mol Cancer Ther Date: 2019-02-20 Impact factor: 6.261
Authors: Giulio Metro; Alfredo Addeo; Diego Signorelli; Alessio Gili; Panagiota Economopoulou; Fausto Roila; Giuseppe Banna; Alessandro De Toma; Juliana Rey Cobo; Andrea Camerini; Athina Christopoulou; Giuseppe Lo Russo; Marco Banini; Domenico Galetta; Beatriz Jimenez; Ana Collazo-Lorduy; Antonio Calles; Panagiotis Baxevanos; Helena Linardou; Paris Kosmidis; Marina C Garassino; Giannis Mountzios Journal: J Thorac Dis Date: 2019-12 Impact factor: 2.895
Authors: Kohei Shitara; Eric Van Cutsem; Yung-Jue Bang; Charles Fuchs; Lucjan Wyrwicz; Keun-Wook Lee; Iveta Kudaba; Marcelo Garrido; Hyun Cheol Chung; Jeeyun Lee; Hugo Raul Castro; Wasat Mansoor; Maria Ignez Braghiroli; Nina Karaseva; Christian Caglevic; Luis Villanueva; Eray Goekkurt; Hironaga Satake; Peter Enzinger; Maria Alsina; Al Benson; Joseph Chao; Andrew H Ko; Zev A Wainberg; Uma Kher; Sukrut Shah; S Peter Kang; Josep Tabernero Journal: JAMA Oncol Date: 2020-10-01 Impact factor: 31.777