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Real-World Treatment Sequences After First-Line Therapy in Metastatic RCC

March 18, 2021


Daniel Geynisman, MD, Fox Chase Cancer Center, Philadelphia, PA, discusses results from a study assessing treatment patterns and sequences in real-world patients with metastatic renal cell carcinoma (RCC) after first-line nivolumab plus ipilimumab or sunitinib monotherapy.

These results were presented at the virtual 2021 ASCO Genitourinary Cancers Symposium.


Hi, my name is Dan Geynisman, and I am a genitourinary oncologist at Fox Chase Cancer Center in Philadelphia. We looked at treatment sequences after first‑line nivolumab and ipilimumab or sunitinib in patients with metastatic clear-cell renal cell carcinoma using real‑world data, and we presented this work in poster fashion at GU ASCO 2021.

The management of metastatic clear-cell kidney cancer has been revolutionized over the last, say, 5 years from tyrosine kinase inhibitors, single agents, to immunotherapy to then immunotherapy plus tyrosine kinase inhibitors.

One of the standard first‑line treatments for patients with intermediate or poor‑risk disease is in fact pure immunotherapy, nivolumab with ipilimumab. This was proven in CheckMate-214 and published previously in the New England Journal of Medicine.

What we wanted to do is looking in the real‑world setting, using Flatiron Database, which covers about 280 oncology practices nationwide, what do patients get treated with in second‑line or even third‑line after receiving nivolumab plus ipilimumab or after receiving sunitinib to just get a sense of the treatment patterns.

The patient population was mimicked to be the same as in CheckMate-214, so newly diagnosed metastatic clear cell RCC patients, and they received either nivolumab with ipilimumab or sunitinib. There were 197 patients who got nivolumab and ipilimumab, 204 who got sunitinib.

Most of them were intermediate or poor risk, but there were about 70 patients who were favorable risk by the IMDC criteria. What, again, we looked at is what are the treatment patterns and outcomes for first‑line therapy and then second‑line patterns and third‑line patterns, and things like time from initial RCC diagnosis to initiation of first‑line therapy, which was approximately 2 months.

Then the median duration of first‑line therapy, which was approximately 4 months. Then, most importantly is what were the second‑line treatment options? Clearly, what we see is that if you receive first‑line nivolumab and ipilimumab, half of the patient in second line received cabozantinib.

The second‑most common was pazopanib and then axitinib. Clearly, TKIs were what was used after ipi/nivo in frontline, and this makes sense, because you're switching agents.

On the other hand, if you were getting sunitinib as front‑line therapy, then the most common about 50%, again, of patients in second‑linereceived nivolumab. Single‑agent PD‑1 immunotherapy, and again, this makes sense as oncologists are trying to switch the mechanism of action.

This was very similar in the intermediate and poor‑risk patients, as well as the favorable‑risk patients. No clearly significant differences there.

Then, if you look at the third‑line options, and the sample size here was quite small, there were only about 82 patients in the study population here. What we see is there's a smattering of different drugs being used.

If you received first‑line nivolumab and ipilimumab, axitinib was used in about 19%. Everolimus and lenvatinib was used in about 18%, and temsirolimus was used in 14%. Then, if you had first‑line sunitinib, it was actually cabozantinib that was in 26.7%.

That makes sense, because remember, a lot of patients after sunitinib receive nivolumab as second‑line. Third‑line, majority receive cabozantinib. Then, if you didn't receive nivolumab in second‑line, then you were receiving it in third‑line, 15% received that.

Just as the NCCN guidelines show, there's a lot of treatment options now for kidney cancer, and so there is not one single path that oncologists choose and follow for second‑line or third‑line treatments, there is a variety.

It really more falls into the classes of drugs, immunotherapy or targeted therapy, and that's how the decision is made, rather than a specific drug, because there are multiple drugs in the same class.

Geynisman DM, Faccone J, Zhang Y, et al. Treatment sequence after first-line nivolumab plus ipilimumab or sunitinib monotherapy in patients with metastatic renal cell carcinoma (mRCC) using real-world data. Presented at: the virtual 2021 ASCO Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 288.

Dr Geynisman reports no relevant financial relationships.

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