Amid Explosion of Novel Agents, Chemo Could Still Have Curative Role in Urothelial Carcinoma

Gina Columbus @ginacolumbusonc
Published Online: Thursday, Dec 15, 2016

Dean Bajorin, MD

Dean Bajorin, MD

Even with 1 FDA approval of an immunotherapeutic agent in urothelial carcinoma—and more expected in the coming months—chemotherapy regimens will continue to play a pivotal part in the treatment of patients with this disease.

Dean Bajorin, MD, professor of Medicine, Memorial Sloan Kettering Cancer Center, discussed the evolving role of cytoxic therapies in bladder cancer in a lecture during the 2016 OncLive State of the Science Summit on Genitourinary Cancers.

“We do know that this is still a curable disease, and that chemotherapy is the mainstay of therapy,” Bajorin says. “Cisplatin is critically important with regard to that type of long-term survival. That has not been replaced with some of the newer drugs that we’re all excited about.”

In an interview, he discusses the ongoing studies exploring new chemotherapy approaches in these patients and how the cytotoxic treatments could still ultimately be replaced with immuno-oncology agents.

OncLive: What were the highlights of your presentation at this meeting?

Bajorin: Historically, bladder cancer has been treated with chemotherapy in metastatic and muscle-invasive disease. In the metastatic setting, there are 2 standards we know of in terms of chemotherapy. For the patients who are somewhat fit, in good physical condition, and have good renal function, cisplatin-based therapy is the standard of care. There are 2 available: 1 is the MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen and the other is the gemcitabine and cisplatin regimen. Both are considered interchangeable with regard to first-line therapy.

Then, there is the patient population that is frailer. This is a disease that happens in the older patient; their kidney function can be compromised and cisplatin is not possible in many of those patients. Therefore, carboplatin-based therapy has been the mainstay of therapy. There have been randomized trials of carboplatin plus gemcitabine showing it as the best tolerated therapy and, in some patients, it can have a substantial benefit.

The sobering aspect of the carboplatin-based studies is that the median survival is still quote poor. We really need to work on that group as well in terms of innovative therapy. The other aspect is that, even in the patients who have stage II or III muscle-invasive disease, the likelihood of death is still extremely high.

All of us know the use of chemotherapy before or after surgery should be a strong consideration. Chemotherapy combined with surgery can, in part, be a survival advantage. Some of the innovations we are seeing are to give chemotherapy in a short period of time at 6 to 8 weeks. Data show that it can still result in a proven benefit, in terms of down-staging a tumor and affecting long-term survival.

What are we seeing in terms of newer data?

Some of the newer data that we are looking at now is trying to identify which patients are likely to respond to chemotherapy. It is trying to identify mutations in DNA damage-repair genes that really confer a high degree of sensitivity to this chemotherapy.

In fact, some data from our center looking at DNA damage-repair genes show that patients who get chemotherapy can have an extraordinary response to chemotherapy. When we do surgery, we actually find very little in the way of the tumor and, sometimes, no tumor at all. Now, there is a movement to identify the patients who have exquisite sensitivity to chemotherapy. You might be able to cure them with just 12 weeks of chemotherapy alone and not have to do surgery. Those studies are ongoing.

The second set of data focuses on the newer drugs. However, the fact of the matter is, immunotherapy still only works in a subset of patients. We really need to identify new drugs and approaches in these patients—and that’s where we get into targeted therapy. There are several targets that are quite viable in this patient population.

The first we are seeing is the FGFR3 mutation, and there are several drugs active in this space. Studies show that up to one-third of patients’ disease is resistant to chemotherapy. Then, they receive a targeted agent, and they can have a major response to just an oral targeted drug. Those studies are ongoing and we are looking forward to how they play out over time.




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