Additional Research Required for Immunotherapy to Replace Chemo in Upfront Bladder Cancer Care

Gina Columbus @ginacolumbusonc
Published Online: Tuesday, Dec 13, 2016

Gopa Iyer, MD

Gopa Iyer, MD

Immunotherapy may be having a moment in the changing landscape of bladder cancer, but expert Gopa Iyer, MD, advises that there is much research to be done before physicians replace chemotherapy with these agents upfront.

The PD-L1 inhibitor atezolizumab (Tecentriq) is FDA-approved for use in patients who progress on cisplatin-based chemotherapy, while clinical trials of the anti–PD-1 agents nivolumab (Opdivo) and pembrolizumab (Keytruda) are both showing promise in the second-line setting, as well. However, first-line trials are already being conducted to evaluate the efficacy of these therapies upfront.

For example, the multicenter, open-label, randomized phase III IMvigor 130 trial is investigating atezolizumab in combination with gemcitabine plus carboplatin versus the chemotherapy regimen alone in untreated patients with locally advanced or metastatic urothelial cancer and are ineligible to receive cisplatin-based therapy (NCT02807636).

In a panel discussion during the 2016 OncLive State of the Science Summit on Genitourinary Cancers, Iyer, an assistant attending physician at Memorial Sloan Kettering Cancer Center, discussed the standard chemotherapy options available for patients with bladder cancer, the ongoing progress with immunotherapy, and the management of immune-related toxicities. Iyer expanded on these topics, including potential frontline therapeutic possibilities, in an interview during the event.

OncLive: The field of bladder cancer has certainly evolved in recent months. What are your thoughts on these advances?

Iyer: For the last 20 years or so, treatment has really been chemotherapy with cisplatin in combination with a number of other chemotherapy agents. While these treatments resulted in responses in a little over 50% of patients, most of these patients will relapse. When we try to give chemotherapy in the second-line setting, the responses are only about 10% to 15%.

There has been a real sea change in the last 6 to 8 months or so with the FDA approval of atezolizumab in patients with metastatic bladder cancer whose disease has already progressed on chemotherapy.

There are standard chemotherapy options available for patients, and we also need to determine when to use immunotherapy in these patients and how to deal with some of the toxicities with immunotherapy.

What toxicities are commonly observed?

The toxicities that most people are recognizing with immunotherapy have been the inflammatory or autoimmune toxicities that some patients are experiencing, such as pneumonitis, hepatitis, and colitis. Most of the time, the treatments for these toxicities have been to hold the drug initially and to treat with a course of steroids—such as prednisone therapy—to quiet the immune system and reduce the inflammation that is going on.

Aside from side effects, what else should community physicians know about treating patients with these agents?

One of the main advantages of immunotherapy has been, when patients do respond, a real durability of response. Although the overall response rates to immunotherapy have not been all that impressive—between 15% and 24% of patients who will have a response—studies are starting to show that probably between 70% to more than 80% of those patients are responding up to 1 year out while they’re on treatment. That really speaks to the durability of response from immunotherapy, but also the tolerability of the treatment.

However, 1 of the things we do see early on in a small percentage of patients is what looks like progression of disease on the first scan that patients have performed while they are on the treatment.

For example, after 3 treatments with atezolizumab, we will check a scan and sometimes it will show that the lesions—the metastatic sites—have grown in size. However, the patents seem to be clinically benefiting from the treatment. They are feeling better, gaining weight, and have better appetite and energy levels. What we think is happening in those cases is pseudoprogression; when we see an increase in these lesions, it is actually the immune cells starting to infiltrate the tumor and attack them. Many of these patients actually will continue on treatment despite what the imaging studies may show, as long as they’re gaining clinical benefit from treatment.

Frequently, what we will see on the second scan after another 3 treatments is that things are stating to shrink again and hopefully will continue to do so. The other thing that is important to keep in mind is recognizing the toxicities early when they do happen. With colitis, patients will often present with diarrhea as the real presenting symptom for that.




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