Atezolizumab Potential Growing Rapidly in Advanced Bladder Cancer

Arjun Balar, MD

Arjun Balar, MD

The recent FDA approval of atezolizumab (Tecentriq) was a significant milestone for the second-line treatment of locally advanced bladder cancer, with even greater potential still on the horizon for the PD-L1 agent, according to Arjun Balar, MD.

“I believe this approval is just the beginning,” said Balar, assistant professor of medicine, Division of Hematology & Oncology, New York University Cancer Institute, NYU Langone Medical Center. “We hope to redefine treatment approaches for all patients with metastatic bladder cancer as immunotherapy plays a stronger and stronger role.”

Atezolizumab was approved in May 2016, based on data from the phase II IMvigor 210 study, as a treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease progressed during or after platinum-based chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery.

The IMvigor 210 study, which enrolled two cohorts of patients, demonstrated an overall response rate (ORR) of 14.8%, regardless of PD-L1 expression, for previously treated patients with mUC. Among patients with PD-L1 expression ≥5%, the ORR was 26%. The PD-L1 assay Ventana PD-L1 (SP142) was concurrently approved as a complementary diagnostic.

The second cohort of the study enrolled patients with mUC who were ineligible for standard cisplatin-based chemotherapy. In this group, atezolizumab had a median survival of 14.8 months. Overall, 24% of patients experienced a reduction in tumor size, with 75% of these responses (21 of 28 patients) still ongoing. The complete response rate was 7%, with the partial response rate reported at 17%.

To better understand the current and potential roles for atezolizumab in bladder cancer,Targeted Oncologyspoke with Balar, who reported findings from the IMvigor 210 trial at the 2016 ASCO Annual Meeting.

TARGETED ONCOLOGY:Can you describe the IMvigor 210 study?

Balar:IMvigor 210 was a study of atezolizumab as therapy in patients with locally advanced or metastatic urothelial cancer. It focused on two cohorts. One group included patients who had previously been treated with platinum-based chemotherapy, that was cohort 2. Cohort 1, which is a study I presented, focused on 119 patients who were previously untreated for metastatic urothelial cancer, or had progressed at least 12 months since completing prior perioperative chemotherapy. Patients were treated with atezolizumab 1200 mg every three weeks until RECIST progression defined by the treating investigator.

TARGETED ONCOLOGY:What should oncologists take away from these findings?

Balar:What we observed in this trial in the 119 patients who were enrolled, was that the objective response rate centrally confirmed was 24%. Additionally, 7% of patients achieved a complete response. When we looked at the responses based on PD-L1 expression, we found that all subgroups benefited in terms of therapy, but importantly patients who had under expression of PD-L1, defined as IC0 or 1, actually had responses as well, including 21% of patients with IC0 achieving objective response, and 8% of those patients achieving a complete response.

TARGETED ONCOLOGY:Based on these results, what role do you see atezolizumab playing in the first-line setting for urothelial cancer?

Balar:Atezolizumab is currently FDA-approved in the second-line setting based off cohort 2. What we saw in cohort 1 was that the response rate was 24% and the estimated median survival was 14.8 months. The data is still immature. This compares very favorably to what we would consider a standard of care for cisplatin ineligible patients, which is gemcitabine and carboplatin, and has a median survival of 9 to 10 months. So certainly we can envision a future where first-line atezolizumab could become a new standard of care.

TARGETED ONCOLOGY:What impact do you think the atezolizumab approval in the second-line setting has had?

Balar:To have a drug approved in this disease after 30 years—3 decades— of research is very exciting. Previously up until this point, cisplatin was the only therapy that has ever been shown to improve survival. In the second-line setting it is a uniformly fatal disease. Response rates with current chemotherapy drugs are less than 10%.

TARGETED ONCOLOGY:Are there any other ongoing trials within immunotherapy in bladder cancer that you are interested in?

Balar:There are a number of different trials now addressing immunotherapy in various disease settings, as well as various combinations. This includes a randomized phase III trial in the second-line setting. It includes randomized phase III trials in the first-line setting with durvalumab and tremelimumab, a CTLA4 and PD-L1 combination. Additionally, we are testing PD-1 or PD-L1 blocking antibodies in localized muscle invasive disease in combination with chemotherapy and radiation. There are other randomized studies looking at atezolizumab or other immune therapies in combination in the first-line setting as well.

TARGETED ONCOLOGY:What do you think are some of the biggest unanswered questions that still remain in this space?

Balar:I think the most unanswered question here is how to understand the biomarker and the role it plays in selecting patients. This seems to be a common question across all solid tumor subtypes, not just bladder cancer. I think the challenges here are to develop a biomarker that can be readily read out in clinics so that the patient sitting in front of us and we’re able to make real time treatment decisions. To date, PD-L1 or PD-1 testing seems to be the fastest that we can get. However, my hope is that in the next several years we will develop biomarkers that are more validated and more useful in the clinic and can actually be useful in a timely fashion.

References

1. Balar AV, Galsky MD, Loriot Y, et al. Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (mUC): primary analysis of IMvigor210 cohort 1.J Clin Oncol. 2016;34(suppl; abstr LBA4500).