How Does Depth of Response Impact Survival in Renal Cell Carcinoma?

When it comes to cancer treatment, it’s important to understand what leads to improvements in survival; knowing these things helps to provide the best outcome for the patient. That’s why medical professionals are often investigating links to better survival. Healio recently reported on a study that discovered a new connection to improved survival in renal cell carcinoma (RCC): depth of response.

What is Depth of Response?

Now, you’re probably asking yourself, what is depth of response? Healio defines it as,

“best percent reduction from baseline in sum of diameters of target lesions.”

Depth of Response in RCC Research

In the past, depth of response has been connected to better outcomes for advanced RCC when used in combination with targeted therapies and/or regimens based on immune checkpoint inhibitors. Aware of this information, Dr. Cristina Suárez and colleagues dove into an exploratory post-hoc analysis. They utilized the data gathered during the CheckMate 9ER trial, which was phase 3 and open-label. The study investigated nivolumab plus cabozantinib versus sunitinib malate in advanced RCC patients who had never received treatment in the past.

The trial itself demonstrated progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in nivolumab plus cabozantinib. Within the exploratory post-hoc analysis of this trial, Suárez and the team divided the participants into groups based on overall response alongside best tumor reduction threshold. The groups were categorized as follows:

  • Partial response 1 (a minimum of 80% response)
  • Partial response 2 (a response between 60% and 80%)
  • Partial response 3 (maximum of 60% response)
  • Stable disease
  • Progressive disease

Six months post-randomization, the researchers evaluated the participants for PFS, OS, time/duration of ORR, and treatment-related adverse events (AEs). Results include the following:

  • More patients in the nivolumab plus cabozantinib group achieved a complete response or fell into partial response groups 1 and 2 than in the sunitinib malate group
  • There was a minimum of a 60% reduction in target lesions in 38% of the nivolumab plus cabozantinib group
    • This can be compared to 17% in the sunitinib malate group
  • Disease progression was observed in 5% of the nivolumab plus cabozantinib group
    • This can be compared to 15% in the sunitinib malate group
  • In both groups, deeper responses were linked to improvements in PFS
    • This observation was also present after 12 months
    • Increased improvements were observed in the nivolumab plus cabozantinib group
  • In general, deeper responses were related to improved OS
  • Within the nivolumab plus cabozantinib group, median duration of response (DOR) saw numerical improvements
  • Stage 3/4 treatment-related AEs were consistent across the various subgroups

After their analysis, the research team noted that there were deeper responses and a lower rate of disease progression within the nivolumab plus cabozantinib group. They also pointed out that depth of response may be a good predictor of prognosis and should be utilized more often.

About Renal Cell Carcinoma (RCC)

RCC is a form of kidney cancer that typically begins with a single tumor in one kidney but easily spreads to the lungs and throughout the body. Symptoms often do not appear until this spread has occurred, which can impact diagnosis and intervention. They include abdominal pain, fatigue, high blood pressure, bloody or discolored urine, weight loss, fever, enlarged testicles, varicose testis vein, and vision abnormalities.

While medical professionals are unsure as to what exactly causes RCC, they do know that there are a number of risk factors. These include smoking and a history of kidney problems. Research has also linked mutations in the TFE 3, PRC, and VHL genes to this cancer. Treatment consists of removing the kidney, bladder, and any necessary surrounding tissue. Other treatment options include Proleukin, chemotherapy, sorafenib, hormone treatments, ablation, and Afinitor.

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