What anti-PD-L1 immunotherapy approval means for urology

FDA approval of a new form of immunotherapy as well as a companion diagnostic test will have a significant impact on patients with the most common type of bladder cancer in the U.S., a leading urologic cancer expert says.       

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In May, the FDA approved atezolizumab (TECENTRIQ) for treatment of locally advanced or metastatic urothelial carcinoma (mUC) that has progressed during or following platinum-based chemotherapy, or has worsened within 12 months of receiving platinum-based chemotherapy before or after surgery.

The FDA also approved VENTANA PD-L1 (SP142) Assay (developed by Roche and available through LabCorp) as a complementary diagnostic for atezolizumab. The assay measures PD-L1 expression in the bladder cancer tissue and has an immune cell scoring algorithm that can help urologists and others identify potentially good candidates for atezolizumab treatment.

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Atezolizumab, the first and only anti-PD-L1 cancer immunotherapy approved by the FDA, was granted an accelerated, or conditional, approval because it helps to fill an unmet need. The drug is the first FDA-approved treatment for people with this specific type of bladder cancer in more than 3 decades, according to a press release from Genentech.

Next: "Finally, now, we have a second-line therapy"

Dr. BlackAtezolizumab is a major breakthrough for patients with bladder cancer and a sign of more good things to come, University of British Columbia, Vancouver urologist Peter Black, MD, told Urology Times.

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“Cisplatin-based combination chemotherapy has been the standard of care for advanced bladder cancer for at least 25 years. When it fails, there are no good alternatives,” said Dr. Black, who is a principal investigator for a Genentech-co-sponsored trial evaluating atezolizumab. “Finally, now, we have a second-line therapy. And this is only the first step. Hopefully, we will be able to use this drug earlier in the care of bladder cancer patients as more trials are completed. It is also noteworthy that this drug was approved first for its use in bladder cancer.”

There is, however, some controversy over the companion assay, according to Dr. Black.

“While the response rate is greatest in patients with high PD-L1 expression, it is still encouraging in patients lacking PD-L1 expression. And these response rates are not yet firmly established,” Dr. Black said. “Developing markers to predict response to atezolizumab and other similar drugs will be very important as the field moves forward-the PD-L1 assay is not the final word.”

The approval of atezolizumab was based on IMvigor 210, an open-label, multicenter, two-cohort phase II study in which researchers studied the drug’s safety and efficacy in patients with locally advanced or metastatic urothelial carcinoma, regardless of PD-L1 expression. More than 300 patients whose disease had progressed during or following platinum-based chemotherapy treatment or who had disease progression within 12 months of treatment with a platinum-based neoadjuvant or adjuvant chemotherapy regimen received a 1,200-mg intravenous dose of atezolizumab on day one of 21-day cycles until unacceptable toxicity or either radiographic or clinical progression.

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Researchers reported that, in a subset of 59 subjects with disease progression following neoadjuvant or adjuvant platinum-containing therapy, atezolizumab shrank tumors in 22% of those patients. The median follow-up was 14.4 months.

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Full results from IMvigor 210 Cohort 1 and updated results from IMvigor 210 Cohort 2 were presented at the recently concluded American Society for Clinical Oncology annual meeting in Chicago. Cohort 1 consisted of patients who had received no prior therapies for locally advanced or metastatic urothelial cancer and who were ineligible for first-line cisplatin-based chemotherapy, according to a press release from Genentech. Cohort 2 consisted of patients whose disease progressed during or following previous treatment with a platinum-based chemotherapy regimen (second-line or later). The primary outcome was objective response rate (ORR).

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In Cohort 1, ORR was 24%. Median overall survival (OS) was 14.8 months, and 12-month landmark OS was 57%. In the updated Cohort 2 results, the researchers observed an ORR of 16%, with median OS of 7.9 months and 12-month landmark OS of 37%.

Possible atezolizumab side effects include pneumonitis, hepatitis, colitis, issues affecting the pituitary, thyroid, adrenal glands, and pancreas, neuropathy and meningoencephalitis, ocular problems, severe infections, and severe infusion reactions.

“It is still only a minority of patients who show an objective response to atezolizumab and the other PD1/PD-L1 inhibitors, but many of those who do respond have durable responses,” Dr. Black said. “The durability of response is the really exciting part. Otherwise, we need to continue searching for additional treatments for those who do not respond.”

Genentech plans to offer patient assistance programs for people taking TECENTRIQ. Doctors can contact Genentech Access Solutions at (888) 249-4918 or get more information at http://www.Genentech-Access.com.

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