Brian M. Shuch, MD, director, Kidney Cancer Program, Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research, University of California, Los Angeles Institute of Urologic Oncology, discusses the impact of the phase III SURTIME study in advanced renal cell carcinoma (RCC).

The SURTIME study took an alternative approach to the CARMENA trial. Instead of patients undergoing cytoreductive nephrectomy upfront and then receiving sunitinib (Sutent), patients in the SURTIME trial received sunitinib (monotherapy) and then cytoreductive nephrectomy. The investigators had a goal of accruing 450 patients but fell short of that goal, says Shuch. The primary endpoint of the study was progression-free survival (PFS), but due to the poor accrual, the primary endpoint was altered to look at PFS at 28 weeks instead.

Although the study did not meet its primary endpoint, investigators noted a difference in overall survival (OS), which served as a secondary endpoint. The patients who had systemic therapy and went on to surgery if they did not have disease progression had an OS at 32 months compared with 15 months in the immediate nephrectomy group, adds Shuch.

However, the study may have been underpowered to show that delayed nephrectomy is beneficial, he cautions. Nonetheless, it shows that with the TKIs, if there are patients who will do poorly with systemic therapy and are going to be put through upfront surgery, some of them are not going to do well. By the time they are ready to receive systemic therapy, they may no longer be a candidate for that approach, as they might be too frail.

Delaying systemic therapy and re-imaging at 3 or 4 months could eliminate that problem and surgery altogether. However, this will have to be studied further as it was a secondary endpoint of a small trial that now has to be considered in the newer targeted immunotherapy era, concludes Shuch.

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Dr. Shuch on the Impact of the SURTIME Trial in Advanced RCC

Brian M. Shuch, MD, director, Kidney Cancer Program, Alvin & Carrie Meinhardt Endowed Chair of Kidney Cancer Research, University of California, Los Angeles Institute of Urologic Oncology, discusses caveats of the combination of avelumab (Bavencio) and axitinib (Inlyta) in frontline advanced renal cell carcinoma (RCC).

Data from the JAVELIN Renal 101 trial which showed an improvement in median progression-free survival with the combination versus sunitinib (Sutent), were striking, Shuch notes. However, sunitinib has been shown to be inferior to several different combinations, including ipilimumab (Yervoy) plus nivolumab (Opdivo) and pembrolizumab (Keytruda) plus axitinib. Single-agent cabozantinib (Cabometyx) has also shown superiority to sunitinib.

Notably, there are still no overall survival (OS) data with avelumab plus axitinib, whereas the other frontline combinations have promising OS data. As such, it would be hard to justify using avelumab plus axitinib versus these other combinations until OS data are published, says Shuch.

In May 2019, the FDA approved avelumab and axitinib for the frontline treatment of patients with advanced RCC.

Brian M. Shuch, MD, director, Kidney Cancer Program, Alvin & Carrie Meinhardt Endowed Chair of Kidney Cancer Research, University of California, Los Angeles Institute of Urologic Oncology, discusses caveats of the avelumab plus axitinib combination in frontline advanced renal cell carcinoma.

Dr. Shuch on Caveats of Avelumab/Axitinib Combination in RCC

Brian M. Shuch, MD, director, Kidney Cancer Program, Alvin & Carrie Meinhardt Endowed Chair of Kidney Cancer Research, University of California, Los Angeles Institute of Urologic Oncology, discusses patient factors to take into consideration when deciding appropriate treatment for patients with advanced renal cell carcinoma (RCC).

This decision-making process needs to be done in a true multidisciplinary setting, Shuch says. If a patient with advanced RCC comes into the clinic with a large primary tumor, low disease burden, and is asymptomatic, they may be a candidate for active surveillance. This is an accepted modality for patients with low-volume disease, Shuch says. Though, surgery is still the preferred approach for eligible patients.

Patients in need of immediate treatment should receive systemic therapy. Moreover, local radiation, palliation, ablation, or metastasectomy can be used to treat distant disease, Shuch notes.

Furthermore, if a patient with significant symptoms does need systemic therapy, risk-stratification can be used to determine whether they should undergo surgery or proceed straight to systemic therapy. Shuch concludes that surgery is still relevant in the new treatment era, but this needs to be discussed with a multidisciplinary team.

Brian M. Shuch, MD, director, Kidney Cancer Program, Alvin & Carrie Meinhardt Endowed Chair of Kidney Cancer Research, University of California, Los Angeles Institute of Urologic Oncology, discusses patient factors to take into consideration when deciding appropriate treatment for patients with advanced renal cell carcinoma.

Dr. Shuch on Considerations for Appropriate Treatment in Advanced RCC

Brian M. Shuch, MD, director of the Kidney Cancer Program, Alvin & Carrie Meinhardt Endowed Chair of Kidney Cancer Research, University of California, Los Angeles Institute of Urologic Oncology, discusses the role of cytoreductive nephrectomy in the treatment of patients with renal cell carcinoma (RCC).

Starting in 2005, this paradigm entered a new era with the approval of VEGF TKIs such as sorafenib (Nexavar) and sunitinib (Sutent), tolerable agents that offer high response rates and promising progression-free survival benefit. That advancement prompted the question of: Would surgery still have a role in the new treatment era? Data from several recent trials have suggested that it was still imperative to remove the primary tumor. With the phase III CARMENA trial, investigators hoped to better define the role of cytoreductive nephrectomy in this space, but that was not the case.

In terms of enrollment for that study, investigators were nonselective in that they allowed patients with very advanced disease or those with intermediate- and poor-risk disease to participate, said Shuch; in fact, 44% of patients enrolled in the trial were poor-risk he added. Patients were randomized to receive either upfront sunitinib or nephrectomy followed by sunitinib. Results showed that sunitinib was noninferior to cytoreductive nephrectomy followed by systemic therapy. However, with immunotherapy making headway in RCC, TKIs are now moving to the second-line setting.

Brian M. Shuch, MD, director of the Kidney Cancer Program, Alvin & Carrie Meinhardt Endowed Chair of Kidney Cancer Research, University of California, Los Angeles Institute of Urologic Oncology, discussed the role of cytoreductive nephrectomy in renal cell carcinoma.

Dr. Shuch on Role of Cytoreductive Nephrectomy in RCC

Brian M. Shuch, MD, assistant professor of Urology and of Radiology and Biomedical Imaging, Yale Cancer Center, discusses the biology of non-clear cell renal cell carcinoma (RCC).

Seventy-five percent of kidney cancers are made up of clear cell histologies, Shuch explains. However, 25% of patients who have variant histologies are lumped into a basket term of non-clear cell RCC. There have been developments in the biology of RCC, but there are about 15 subtypes. Therefore, it is a disservice to patients with these non-clear cell subtypes to be lumped into 1 group, he adds.

Additionally, Shuch is interested in further categorizing these subtypes with more meaningful terminology, because these different kidney cancers have little in common with one another, aside from originating from the same organ.

Brian M. Shuch, MD

Articles

Dr. Shuch on the Impact of the SURTIME Trial in Advanced RCC

Dr. Shuch on Caveats of Avelumab/Axitinib Combination in RCC

Dr. Shuch on Considerations for Appropriate Treatment in Advanced RCC

Dr. Shuch on Role of Cytoreductive Nephrectomy in RCC

Dr. Shuch on Biology of Non-Clear Cell RCC