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Researchers Poised to Expand on Exciting Advancements in RCC

Gina Columbus @ginacolumbusonc
Published: Wednesday, Aug 24, 2016

Mayer Fishman, MD

Mayer Fishman, MD

The therapeutic options for renal cell carcinoma (RCC) have drastically improved over the last several years; however, work still needs to be done to determine how to optimally sequence the plethora of available agents, according to Mayer Fishman, MD.

There are other challenges that also need to be addressed, says Fishman, such as understanding triggers to therapy and identifying new biomarkers for treatments. Fishman, a medical oncologist at Moffitt Cancer Center, highlighted the most recent advances in the field of RCC during his lecture at the 2016 OncLive State of the Science Summit on Genitourinary Cancers.

In an interview with OncLive during the meeting, Fishman discussed the therapeutic landscape in RCC and the next steps needed to further advance the field.

OncLive: There has been a lot of excitement in kidney cancer over the last couple of years. What should be highlighted about the agents that are now available?

Fishman: There are 3 main medicines in the kidney cancer therapies. There is the VEGF group, the immunotherapy group, and the mTOR group. There have been a few approvals in the last several months.

In the immunotherapy group, nivolumab (Opdivo) was approved as an anti–PD-1 drug. It got some other indications, and now it is approved for kidney cancer use.

In the VEGF group, cabozantinib (Cabometyx) was approved, which blocks c-MET as well as VEGF, so that is a difference. Lenvatinib (Lenvima) blocks VEGF and FGFR1, and then lenvatinib was given in combination with everolimus (Afinitor). That 2-part combination was the superior one. With those 3 treatments, each of them had been compared with everolimus; each of them showed a survival advantage. Those are some treatments that are now available.

That comes in addition to other VEGF medicines that are available, such as sunitinib (Sutent), sorafenib (Nexavar), pazopanib (Votrient), axitinib (Inlyta), and bevacizumab (Avastin), and other mTOR medicines, such as everolimus and temsirolimus (Torisel), and other immunotherapies such as interleukin-2 (IL-2). There are actually 10 different medicines around for treating metastatic kidney cancer. It does make for a more complicated scene, but there are going to be select patients who do particularly well with 1 or another, so I am optimistic that that’s going to help patients.

What is a key takeaway about triggers and options for upfront therapy?

The first issue is always going to be managing symptomatic disease. If there is no symptomatic disease, some things that might become symptomatic are brain disease or an impending fracture, and the next issue is typically going to be a nephrectomy. Patients with a lot of bulk of metastatic disease will often get a deferred nephrectomy or a limited renal reserve.

On the other hand, if the dominant amount of disease were in the kidney, most of those patients would look at an upfront nephrectomy as initial treatment.

Our next issue is timing of starting medical therapy. If there is relatively rapid growth, that forces the issue. Some patients who have relatively slow growth, or is slow compared with other comorbid problems, deferring start of therapy may make more sense for them.

The trigger to start on active treatment might be a pattern of growth; it might be a sense of anxiety or missed opportunity for not starting immediately. It could be an obvious growth pattern where there’s just not going to be a long window to delay treatment. Not being on treatment, of course, has a lot of advantages as far as side effects. However, it can seem like a mixed opportunity—in fact, it can be a missed opportunity for some patients.

As far as which treatment to start with, it’s going to have to be individualized. There are going to be some patients who do well with initial treatment with immunotherapy, such as IL-2. Some patients do well with initial treatment with checkpoint inhibitor therapy, although that’s currently off-label for nivolumab as initial treatment.

We do have the research study that accommodates upfront treatment for that. Some patients will get initial therapy with the VEGF medicines. To that extent, VEGF agents have been compared directly to one another; there is not an obvious advantage with one or the other. Some of them have a label, which alludes to second-line therapy such as axitinib, lenvatinib, or cabozantinib. I don’t think anyone would expect that it wouldn’t be active as a first-line therapy, as well. I expect issue of initial or subsequent therapy to evolve.




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