Immunotherapy Beats Chemotherapy for Advanced Bladder Cancer Patients

The immunotherapy drug pembrolizumab (Keytruda) is the first therapy of any kind to improve survival in patients whose metastatic bladder cancer worsened after treatment with platinum-based chemotherapy. Keytruda proved so much better than chemotherapy in this “second-line” use that an international clinical trial was halted when the advantage became apparent.

 Joaquim Bellmunt
Joaquim Bellmunt, MD, PhD, principal investigator on the Keytruda clinical trial.

“This is very good news; no real survival improvement had ever been demonstrated with a second-line treatment for these patients,” says Joaquim Bellmunt, MD, PhD, director of the Bladder Cancer Center at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC).

“This is the first trial of any compound to beat chemotherapy in the history of bladder cancer,” notes Toni Choueiri, MD, director of Dana-Farber’s Lank Center for Genitourinary Oncology. “It may be a new standard in bladder cancer.”

Keytruda is one of a new class of immunotherapy drugs known as PD-1 checkpoint blockers, and is being tested in 30 different types of cancer. It’s the drug that shrank Former President Jimmy Carter’s metastatic melanoma to the point where it was undetectable.

Bellmunt is principal investigator of the phase 3 clinical trial known as KEYNOTE-045 sponsored by Keytruda’s maker, Merck, that involves 542 patients with urothelial (bladder) cancer that had spread within the body and was inoperable. They had been given platinum-containing chemotherapy agents, but the disease had recurred or gotten worse. There is no approved treatment for such patients, and giving additional chemotherapy hasn’t been found to halt the cancer’s growth or help patients live longer.

In the KEYNOTE-045 trial, the patients were randomized to receive Keytruda or chemotherapy of the physicians’ choice – paclitaxel, docetaxel, or vinflunine. The questions were whether patients getting Keytruda experienced longer periods before the cancer progressed, and if they lived longer than those who received chemotherapy.

In a statement on Oct. 21, Merck said an independent committee monitoring the results recommended that the trial be halted after observing that the statistical benefit of survival for Keytruda-treated patients, as specified in the trial design, was met. Chemotherapy-treated patients were allowed to switch to Keytruda at the time of chemotherapy progression.

Further details of the results will be presented at scientific meetings and published in journals.