Predicting who may benefit from new bladder cancer drug
The story of Lou Pagano's bladder cancer diagnosis was typical, starting as blood in his urine. Testing showed his tumor growing into the bladder wall, a sign of more advanced disease. Pagano, an affable former New Yorker now living in Montgomery County, went through several rounds of intravenous chemotherapy to shrink the tumors before doctors removed his bladder and created a new urine reservoir out of part of his intestines. For many patients, this course of treatment cures the cancer. But when he was re-evaluated several months after surgery, tumors showed up in diagnostic scans of his liver, lymph nodes, and bones.
Therapy for patients with bladder cancer that has metastasized has included the same drugs for 30 years, with limited success. Cisplatin-based intravenous chemotherapy is recommended before bladder removal, or if cancer metastasizes, but does not control the tumor in all patients.
Just last week, the prospect for bladder cancer patients improved. An immunotherapy developed by Genentech/Roche was approved by the Food and Drug Administration (FDA). The drug, called Tecentriq (atezolizumab), belongs to a class of cancer therapies called checkpoint inhibitors that essentially turn the patient's immune system into a cancer-fighting weapon. The clinical study that supported the FDA's decision to approve the drug, showed a response rate of 15 percent in patients who have already received chemotherapy for their bladder cancer. The response rate with other therapies was only 10 percent, and didn't last as long.
Patients in the atezolizumab trial had responses lasting for a median follow up of nearly 12 months, and the data in this report followed patients only for a little over a year, so the response time could be better than the numbers suggest.
Moreover, many patients' tumors completely disappeared, which is nearly unheard of in cancer trials for disseminated, drug-resistant bladder cancer. For many patients on the study, the side effects they experienced on atezolizumab were significantly milder than those with chemotherapy. However, some patients do experience harsh side effects with this class of immunotherapies, and these therapies are costly, so it would be useful to know which patients may be more likely to respond ahead of time. (Participants in the trial receive the therapy free of charge.)
After Pagano's cancer spread, he became one of the many Jefferson patients to enroll in the Genentech/Roche clinical trial, the results of which led to this change in standard of care. As part of the trial, we provided patient tumor samples in order to validate tests that predict response to atezolizumab. This "complementary diagnostic" that Roche/Genentech developed detects the molecule PD-L1, whichis the target for this drug. Jefferson pathology is one of seven sites across the U.S. that participated in the testing access readiness program for the reading and reporting of the PD-L1 antibody on bladder cancer.
Lou Pagano is not free of cancer, but his tumor is no longer growing. Unlike the difficult and lasting side effects from some of his chemotherapy, he says his only problem on Tecentreq is that his fingers lock up occasionally and he's tired for a few days after treatment. But he's been able to see his fourth grandchild, who was born while Pagano was in treatment, grow up to be a delightful 2-year-old terror. He continues to be a support to others with bladder cancer through his work with the Bladder Cancer Advocacy Network, BCAN.
Jean Hoffman-Censits, M.D., is a bladder cancer researcher and expert, and Director of the Multidisciplinary Genitourinary Cancer Clinic at the Sidney Kimmel Cancer Center at Jefferson. Charalambos Solomides, M.D., is Associate professor of Pathology, Anatomy and Cell Biology and Director of Cytopathology and Immunohistochemistry Lab at the Sidney Kimmel Medical College at Thomas Jefferson University
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