Mohamad Ezzeddine Allaf, MD, urologist-in-chief, Johns Hopkins Hospital, professor of Urology, Johns Hopkins Medicine, discusses several key considerations when interpreting and extrapolating initial results from the phase 3 PROSPER-RCC trial in renal cell carcinoma.

The PROSPER-RCC trial evaluated nephrectomy with nivolumab vs the standard approach of nephrectomy plus postoperative follow-up and monitoring in patients with localized RCC. Results from the phase 3 study demonstrate that perioperative nivolumab did not significantly improve recurrence-free survival at 16 months median follow-up vs the standard observation arm.

Although the trial was ultimately negative, caution should be exercised when interpreting results, Allaf begins. Aspects of the trial design, patient characteristics, and patient subgroups from the PROSPER-RCC trial may provide insight on the efficacy of the treatment strategy. Moreover, treatment investigators are continuing to try to interpret the implications of these data Investigators continue to identify areas of improvement for future neoadjuvant RCC trials, Allaf explains.

PROSPER-RCC was the first trial of its kind, and featured a progressive trial design, Allaf says. Patients received the neoadjuvant dose of nivolumab followed by nephrectomy, and then adjuvant therapy. However, some patients who did not progress to surgery, receive neoadjuvant therapy, or receive the adjuvant component may have been ineligible for these treatments, Allaf notes.

Additionally, the trial measured patients' overall survival (OS) and recurrence-free survival as key secondary endpoints. Notably, a biopsy component was successfully included, which enabled large amounts of histopathological biomarker data to be obtained from patients who underwent neoadjuvant treatment, Allaf says. Overall, immature OS data currently prevents researchers from making a conclusive statement on patients' quality of life, Allaf states.

Subset analyses are continuing to be study in order to better understand what next steps should be taken as a field, Allaf concludes.

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Mohamad Ezzeddine Allaf, MD, discusses several key considerations when interpreting and extrapolating initial results from the phase 3 PROSPER-RCC trial in renal cell carcinoma.

Dr. Allaf on Evaluating the PROSPER-RCC Trial Results in RCC

Mohamad Ezzeddine Allaf, MD, urologist-in-chief, Johns Hopkins Hospital, professor of Urology, Johns Hopkins Medicine, discusses the results of perioperative nivolumab (Opdivo) vs observation in patients with renal cell carcinoma (RCC) who undergo nephrectomy.

The phase 3 PROSPER trial (NCT03055013) compared nephrectomy with nivolumab vs the standard approach of nephrectomy plus post-operative follow-up and monitoring in patients with RCC.

Findings presented at the 2022 ESMO Congress showed that the study did not meet its primary end point of event-free survival (EFS), Allaf says. At a preplanned interim analysis, the hazard ratio for nivolumab vs observation was 0.96, Allaf continues, adding that the EFS curves remained similar at a median follow up of approximately 16 months.

The trial enrolled over 800 patients and had 3 preplanned futility analyses, based on the available information for follow-up events comprising recurrences and deaths, Allaf explains. At this planned interim analysis of inefficacy, approximately 71% of EFS events were available. The efficacy analysis was presented to the safety monitoring committee, which recommended the release of the results for futility, Allaf concludes.

Mohamad Ezzeddine Allaf, MD, discusses the results of perioperative nivolumab vs observation in patients with renal cell carcinoma who undergo nephrectomy.


Mohamad Ezzeddine Allaf, MD

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Dr. Allaf on Evaluating the PROSPER-RCC Trial Results in RCC

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