Dose-limiting Urinary Toxicity With Pembrolizumab Combined With Weekly Hypofractionated Radiation Therapy in Bladder Cancer.

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.

• Publication year

  2018

• Venue

  International Journal of Radiation Oncology, Biology, Physics

• Publication date

  2018-08-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.ijrobp.2018.04.070PMID 30012528
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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