Dose-limiting Urinary Toxicity With Pembrolizumab Combined With Weekly Hypofractionated Radiation Therapy in Bladder Cancer.
Loading...
Embargo End Date
ICR Authors
Authors
Tree, AC
Jones, K
Hafeez, S
Sharabiani, MTA
Harrington, KJ
Lalondrelle, S
Ahmed, M
Huddart, RA
Jones, K
Hafeez, S
Sharabiani, MTA
Harrington, KJ
Lalondrelle, S
Ahmed, M
Huddart, RA
Document Type
Journal Article
Date
2018-08-01
Date Accepted
2018-04-24
Abstract
There is currently significant interest in the potential benefits of combining radiation and immune checkpoint blockade (ICB) to stimulate both regional and distant abscopal immune responses. In melanoma and lung cancer, patients who have received radiation therapy during ICB appear to have prolonged survival. The PLUMMB trial (Pembrolizumab in Muscle-invasive/Metastatic Bladder cancer) (NCT02560636) is a phase I study to test the tolerability of a combination of weekly radiation therapy with pembrolizumab in patients with metastatic or locally advanced urothelial cancer of the bladder. In the first dose-cohort, patients received pembrolizumab 100 mg 3-weekly, starting 2 weeks before commencing weekly adaptive bladder radiation therapy to a dose of 36 Gy in 6 fractions. The first dose-cohort was stopped after 5 patients, having met the predefined definition of dose-limiting toxicity. Three patients experienced grade 3 urinary toxicities, 2 of which were attributable to therapy. One patient experienced a grade 4 rectal perforation. In view of these findings, the trial has been paused and the protocol will be amended to reduce radiation therapy dose per fraction. The authors advise caution to those combining radiation therapy and ICB, particularly when radiation therapy is given at high dose per fraction for pelvic tumours. The PLUMMB trial met the protocol-defined definition of dose-limiting toxicity and will be amended to reduce radiation therapy dose.
Citation
International journal of radiation oncology, biology, physics, 2018, 101 (5), pp. 1168 - 1171
Source Title
Publisher
ELSEVIER SCIENCE INC
ISSN
0360-3016
eISSN
1879-355X
Research Team
Clinical Academic Radiotherapy (Huddart)
Gynaecological Cancer
Lung Radiotherapy
Targeted Therapy
Gynaecological Cancer
Lung Radiotherapy
Targeted Therapy