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ESMO 2016: Immunotherapy Shows Promising Results in First- and Second-Line Treatment of Metastatic Bladder Cancer in Two Trials

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Key Points

  • In a study evaluating pembrolizumab as first-line therapy in cisplatin-ineligible patients with metastatic or locally advanced bladder cancer, objective response rate was 24%; the biomarker cut point to identify patients who are most likely to respond to the drug was determined to be 10% or greater total PD-L1 expression in immune cells or tumor cells; median duration of response has not yet been reached; and treatment was well-tolerated.
  • In a study evaluating nivolumab in patients with metastatic bladder cancer who have progressed, despite first-line platinum-based chemotherapy, the objective response rate was 19.6%; the median duration of response has not yet been reached, with a median follow-up of 7 months; and in tumors expressing higher and lower levels of PD-L1, the objective response rate was above that achieved historically with chemotherapy.

Immunotherapy has shown promising results in the first- and second-line treatment of metastatic bladder cancer in two phase II trials presented by Galsky et al and Balar et al at the 2016 European Society for Medical Oncology (ESMO) Congress in Copenhagen (Abstracts LBA31_PR and LBA32_PR, respectively).

Up to half of patients with metastatic bladder cancer are not eligible for survival-prolonging first-line treatment with cisplatin-based chemotherapy. Survival in these patients is just 9 to 10 months with currently available alternative chemotherapy.

KEYNOTE-052        

The phase II KEYNOTE-052 trial evaluated the efficacy and safety of programmed cell death protein 1 (PD-1) blockade with pembrolizumab (Keytruda) as first-line therapy in cisplatin-ineligible patients with metastatic or locally advanced bladder cancer. Researchers presented the preliminary analysis of the first 100 patients enrolled in the trial.

The primary endpoint of objective response rate was 24%. The biomarker cut point to identify patients who are most likely to respond to the drug was determined to be 10% or greater total programmed cell death ligand 1 (PD-L1) expression in immune cells or tumor cells. Thirty patients had this level of expression, of whom 11 (37%) responded to treatment. The median duration of response has not yet been reached, and treatment was well tolerated.

Lead author Arjun Balar, MD, Assistant Professor at NYU Langone Medical Center, said, “Pembrolizumab has substantial activity with a favorable safety profile as first-line therapy in cisplatin-ineligible patients with metastatic bladder cancer. The biomarker cut point will need to be validated in the larger study population but seems to identify patients most likely to respond to pembrolizumab well. Immunotherapy is rapidly redefining our treatment approach for patients facing this dreadful disease.”

CheckMate 275

For several decades, there had been no global standard of care for the second-line treatment of patients with metastatic bladder cancer who have disease progression despite platinum-based chemotherapy, until the recent development of immune checkpoint blockade. In another study, the phase II CheckMate 275 trial assessed the activity and safety of the PD-1 inhibitor nivolumab (Opdivo) in 270 patients with metastatic bladder cancer who have disease progression, despite first-line platinum-based chemotherapy. CheckMate 275 is the largest study of a PD-1 inhibitor in bladder cancer reported to date.

In the 265 patients who could be evaluated for efficacy, the primary endpoint of objective response rate was 19.6%. The median duration of response has not yet been reached, with a median follow-up of 7 months. In both patients with tumors expressing higher and lower levels of PD-L1 (including those with less than 1% PD-L1), the objective response rate was above that achieved historically with chemotherapy.

“These data are being submitted to support registration of nivolumab for patients with metastatic urothelial cancer that has progressed despite platinum-based chemotherapy, an indication for which the U.S. Food and Drug Administration has granted Breakthrough Therapy designation to nivolumab,” said lead author Matthew Galsky, MD, Professor of Medicine at the Icahn School of Medicine at Mount Sinai. “Immune checkpoint blockade has become the most promising approach for these patients.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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