Future Strategies in Kidney Cancer Treatment - Episode 12

Kidney Cancer: Non-Clear Cell Histology


James J. Hsieh, MD, PhD: Have we improved the care of non—clear cell kidney cancer in patients? About 70% of kidney cancer is clear-cell kidney cancer. So, when we talk about kidney cancer, we always talk about clear-cell kidney cancer patients, and they represent about 80% of the metastatic kidney cancer patients that we deal with. The remaining 20% are metastatic disease, and about 15% of them are a papillary type of kidney cancer. Some of them are chromophobe, and then the other rare ones—SDHB, TFE3, collecting duct medullary type—those are rare diseases.

So, we have this consortium and this effort from a patient advocate. We established something, a website called rarekidneycancer.org. The idea is that basically these patients are so few, now how do we provide the best care for them? As I told you in a very rosy way, we moved from a dark age to a modern age to a golden age, but a non—clear cell patient is still in almost a dark age to me. That’s very, very sad. What happened was, as I said, in the past, the median survival for a metastatic clear-cell patient was about 15 months. Now we’re almost at 30 months. We’re going to move it to 60 months.

But for non—clear cell patients, especially papillary patients, it was 12 months, 12 months, 12 months. Nothing changed. So, we know they work better on the anti-VEGF treatment better than mTOR inhibitors. And a good thing to know is that the trial that we conducted using Avastin/everolimus showed efficacy. Again, showing the combination is very important for kidney cancer.

But it’s not standard and everybody still tried to figure out how to treat nonmetastatic kidney cancer patients. I think the doctor’s community is trying to do this by accruing patients to the right trials. But I think we also need to raise the patients’ awareness and engage them to participating. And also, their local treatment oncologists should be educating them so we can actually move in the field faster that way.

Thomas Hutson, DO, PharmD, FACP: Non—clear cell renal cell carcinoma has been an enigma. It has been a very difficult cancer to treat, and most of the drugs that we have available for us to choose in clinics have been predominately designed in the clear-cell histologic subtype. There are several agents, however, that hold some promise for non–clear cell histologies. I’m personally the PI of a phase II trial that is ongoing that looks at the combination of lenvatinib and everolimus in this patient population.

Cabozantinib, being a c-MET inhibitor, also may have unique opportunities and activity in this cancer, as well as I-O therapies. Nivolumab has launched clinical studies in non—clear cell histologies. In addition, there are other TKIs in development in phase III trials. One of them is called the phase III SAVOIR trial, which Dr. Toni Choueiri is evaluating with savolitinib, which is a c-MET FGF inhibitor for this cancer.

Martin H. Voss, MD: For patients with papillary histologies, there are combination regimens that appear to be promising based on phase II data that have been presented by different groups. The combination of bevacizumab/erlotinib has been tested by the NCI group in patients with papillary kidney cancers, including a high proportion of patients with underlying hereditary predisposition syndromes, specifically hRCC syndrome. A high level of clinical activity was seen particularly in that space.

Our own group has reported on a similar combination in this patient population. And also, we have published on the combination of bevacizumab plus everolimus, which, in the first-line space, we also found to be highly effective, particularly for patients with major papillary components found in their tumors.

Transcript Edited for Clarity