The CHASIT study: sequential chemo-immunotherapy in patients with locally advanced urothelial cancer – a non-randomized phase II clinical trial

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
8 Downloads (Pure)

Abstract

Background: Patients with locally advanced irresectable or clinically node positive urothelial cancer (UC) have a poor outcome. Currently, these patients can only be cured by receiving induction chemotherapy and, if an adequate radiological response is obtained, radical surgical resection. Long-term survival, however, strongly depends on the absence of residual tumor in the surgical resection specimen, i.e. a pathological complete response (pCR). The reported pCR rate following induction chemotherapy in locally advanced or clinically node-positive UC is 15%. The 5-year overall survival rate for patients achieving a pCR is 70–80% versus 20% for patients who have residual disease or nodal metastases. This clearly demonstrates the unmet need to improve clinical outcome of these patients. Recently, the JAVELIN Bladder 100 study demonstrated an overall survival benefit of sequential chemo-immunotherapy in patients with metastatic UC. The CHASIT study aims to translate these findings to the induction setting by assessing the efficacy and safety of sequential chemo-immunotherapy in patients with locally advanced or clinically node-positive UC. In addition, patient biomaterials are collected to investigate biological mechanisms of response and resistance to chemo-immunotherapy. Methods: This multicenter, prospective phase II clinical trial includes patients with stage cT4NxM0 or cTxN1-N3M0 UC of the bladder, upper urinary tract or urethra. Patients who do not experience disease progression after 3 or 4 cycles of platinum-based chemotherapy are eligible for inclusion. Included patients receive 3 cycles of anti-PD-1 immunotherapy with avelumab followed by radical surgery. Primary endpoint is the pCR rate. It is hypothesized that sequential chemo-immunotherapy results in a pCR rate of ≥ 30%. To obtain a power of 80%, 64 patients are screened and 58 patients are included in the efficacy analysis. Secondary endpoints are toxicity, postoperative surgical complications, progression-free, cancer-specific and overall survival at 24 months. Discussion: This is the first study to assess the potential benefit of sequential chemo-immunotherapy in patients with locally advanced or node positive UC. If the primary endpoint of the CHASIT study is met, i.e. a pCR rate of ≥ 30%, a randomized controlled trial is foreseen to compare this new treatment regimen to standard care. Trial registration: NCT05600127 at Clinicaltrials gov, registered on 31/10/2022.

Original languageEnglish
Article number539
JournalBMC Cancer
Volume23
Issue number1
DOIs
Publication statusPublished - 13 Jun 2023

Bibliographical note

Funding Information:
In each participating center, the principal investigator will be responsible for recruitment, adherence to the study protocol and follow-up of the included patients. Members of the CHASIT study group: Dr. A.G. van der Heijden, urologist, Radboud University Medical Center, Nijmegen. Dr. N. Mehra, medical oncologist, Radboud University Medical Center, Nijmegen. Dr. J.A.P. Leijte, urologist, Amphia Hospital, Breda. Dr. H.M. Westgeest, medical oncologist, Amphia Hospital, Breda. Dr. T.J. Smilde, medical oncologist, Jeroen Bosch Hospital, ‘s Hertogenbosch. Dr. S. van der Meer, urologist, Jeroen Bosch Hospital, ‘s Hertogenbosch.

Funding Information:
The CHASIT study is financially supported by Merck (CrossRef Funder ID: https://doi.org/10.13039/100009945 ), as part of an alliance between Merck and Pfizer. The funding body has been involved in the study design and selection of primary and secondary outcomes. The funding body has no role in data collection, data analysis nor data interpretation. Merck is the manufacturer of the study drug avelumab. Merck (CrossRef Funder ID: https://doi.org/10.13039/100009945 ) and Pfizer reviewed this manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors.

Publisher Copyright:
© 2023, The Author(s).

Fingerprint

Dive into the research topics of 'The CHASIT study: sequential chemo-immunotherapy in patients with locally advanced urothelial cancer – a non-randomized phase II clinical trial'. Together they form a unique fingerprint.

Cite this