Apolo Discusses Promising Immunotherapy Combos in Bladder Cancer

Andrea Apolo, MD

Andrea Apolo, MD

Andrea Apolo, MD, presented promising early data at the 2017 Genitourinary (GU) Cancers Symposium demonstrating the activity and safety of cabozantinib and nivolumab (Opdivo), with or without ipilimumab (Yervoy), in bladder cancer and other advanced genitourinary cancers.¹

Apolo, a medical oncologist at the National Cancer Institute and chief of the bladder cancer section of the Genitourinary Malignancies Branch, expressed her excitement about immunotherapy combinations in bladder cancer in an interview withTargeted Oncologyat the GU Symposium.

“Bladder cancer is a devastating malignancy when it’s metastatic—the overall survival of patients with advanced disease is about 14 months. But I feel like that is changing now with the new approvals and with the new efficacy that we have seen with immunotherapy, and I think that we can do even better than that with these combination therapies that we are testing right now,” said Apolo.

Apolo also shared results at the GU symposium for the immunotherapy avelumab in patients with metastatic urothelial carcinoma from a pooled analysis of 2 cohorts from the phase 1b JAVELIN trial.²

In her interview withTargeted Oncology, Apolo reflected on the findings from these trials and the future of immunotherapy in bladder cancer.

TARGETED ONCOLOGY:Could you provide an overview of the study of cabozantinib/nivolumab with or without ipilimumab?

Apolo:

We conducted a phase I study of cabozantinib with nivolumab and ipilimumab. Initially, we did a monotherapy phase II trial of cabozantinib by itself in patients with metastatic bladder cancer and we found activity. We also looked at immune subsets to understand the microenvironment of the patients being treated with cabozantinib.

We saw that cabozantinib has immunomodulatory properties—it changes T-regulatory cells, myeloid-derived suppressor cells. We thought this was a good rationale for combining it with immunotherapy with checkpoint inhibition. So, we have these combinations of cabozantinib and nivolumab, and cabozantinib, nivolumab, and ipilimumab here at ASCO GU 2017. We presented our phase I results from 48 patients treated.

The patients were metastatic bladder cancer patients, but the study also included other patients with genitourinary malignancies such as prostate cancer, renal cell carcinoma, and many patients with rare histologies such as RCC sarcomatoid, bladder cancer urachal adenocarcinoma, squamous cell carcinoma of the bladder, penile cancer, and germ-cell tumor patients. 

TARGETED ONCOLOGY:What did the results show?

Apolo:

We found that the combination was safe, there was known toxicities from cabozantinib, nivolumab, and ipilimumab, but they were not additive. The combination was tolerable and we have many patients that remained on-study for over a year.

We also found that the combination was very active. Overall, for the group of patients that were treated, we found a response rate of 30%. And when we looked at the bladder cancer patients with the combination of cabozantinib and nivolumab we found a response rate of 44%

TARGETED ONCOLOGY:What are the next steps with these combinations?

Apolo:

The next steps with these combinations are to test them in larger trials, looking at specific tumor types. We hope to do that in bladder cancer and in kidney cancer. Right now, we have an expansion cohort of metastatic bladder cancer patients being treated with both cabozantinib/nivolumab and cabozantinib/nivolumab/ipilimumab. We also have an expansion cohort for RCC cells. We really want to understand—now that we know that the combinations are safe—the efficacy of the doublet and the triplet combinations.

I hope that in looking at this combination that, although there was a lot of concern about the toxicity, we found that the combination was well tolerated. So, I think that this may be a combination that we could potentially use in the future for these patients to better improve upon the outcomes.

TARGETED ONCOLOGY:What do you foresee the role of immunotherapy being in the future of bladder cancer treatment?

Apolo:

Here at the GU Symposium, we present a pooled analysis of 2 cohorts that we had in metastatic bladder cancer patients treated with avelumab, which is a PD-L1 inhibitor. We had a 44-patient cohort of metastatic bladder cancer patients, and then a 200-patient cohort, and we pooled the data together. Looking at the patients who had a follow-up of greater than 6 months—about 150 patients—we found an overall response rate of 17.6%, so that was very exciting. We also found in patients with poor prognostic features the avelumab was very well tolerated.

Currently, there is a phase III trial of avelumab being tested in patients with metastatic bladder cancer in the maintenance setting. So, these are patients after receiving first-line therapy with chemotherapy and if they have a response, they go on to received avelumab therapy versus observation to see if there is a change in overall outcome.

References:

1. Apolo A, Mortazavi A, Stein MN, et al. A phase I study of cabozantinib plus nivolumab (CaboNivo) and ipilimumab (CaboNivoIpi) in patients (pts) with refractory metastatic urothelial carcinoma (mUC) and other genitourinary (GU) tumors.J Clin Oncol35, 2017 (suppl 6S; abstract 293).
2. Patel MR, Ellerton JA, Infante JR, et al. Avelumab in patients with metastatic urothelial carcinoma: Pooled results from two cohorts of the phase 1b JAVELIN Solid Tumor trial.J Clin Oncol35, 2017 (suppl 6S; abstract 330).

I think it’s a new treatment paradigm in bladder cancer. Immunotherapy is effective and I think right now, we are looking into doing better than what we're doing now and improving upon the response rate by using combination therapy.