KEY TAKEAWAYS
- The Phase III PROSPER study (NCT03055013) was a randomized trial comparing surgery alone to neoadjuvant Nivolumab (nivo) followed by adjuvant nivo in patients with high-risk RCC.
- In this 2-arm study, arm I received the study drug while the arm II underwent partial or radical nephrectomy.
- The primary outcome was RFS, and secondary outcomes included clear cell RCC RFS, overall survival (OS), and quality of life indicators.
- The results of the study showed that perioperative nivo did not improve RFS or OS, additionally, adverse events were more frequent in the nivo arm.
PROSPER phase III trial was conducted to assess the effectiveness of neoadjuvant nivo in priming the immune system prior to nephrectomy followed by adjuvant nivo in patients with high-risk renal cell carcinoma (RCC), as compared to surgery alone.
Patients with clinical stage ≥T2 or TanyN+ RCC who were scheduled for nephrectomy were included in the entry requirements. (partial or radical). If the patient could be declared “no evidence of disease” within 12 weeks of surgery, select oligometastatic disease was allowed. Nivo was given (480 mg IV q4 weeks) in the investigational arm with 1 dosage previous to surgery and 9 adjuvant doses following.
Surgery was followed by observation without a placebo in the control group. Only the nivo arm needed a baseline tumour biopsy. Regardless of histology, the primary outcome was recurrence free survival (RFS). Clear cell RCC RFS, overall survival (OS), and quality of life indicators are examples of secondary outcomes.
819 patients were randomly assigned between postoperative nivo (n=404) or surgery alone (n=415). 83% of patients had clear cell RCC, and the clinical stages at enrollment were 53% cT2, 47% cT3-4, 17% cN1, and 4% cM1. Due to the trial’s failure, DSMC terminated it early.
RFS(HR: 0.97; 95% CI: [0.74 – 1.28]; P1-sided = 0.43) was comparable between the groups.RFS median was not attained. Despite not being fully developed at the time of analysis, OS did not show a statistically significant difference between research arms (HR: 1.48; 95% CI: [0.89 – 2.48]; P1-sided = 0.93). Similar withdrawal rates of around 12% (48/404 patients in the nivo arm vs. 50/415 in the surgery alone arm) were seen in both groups.
Compared to 6% in the control group, 20% of patients who received nivo had at least one Grade 3–4 AE that could be linked to the drug. Kidney damage, rash, and elevated lipase were the most frequent grade 3–4 adverse events (AEs) associated with therapy. In the nivo arm, there were 15 (4%) deaths from RCC, and in the surgery alone group, there were 18 (4%) deaths from RCC.
In conclusion, the perioperative administration of nivo did not improve RFS in RCC patients at high risk for recurrence. Nevertheless, OS data remain immature, and ongoing subset analyses, including risk stratification by pathologic stage, may provide further insights.
Source:https://cslide.ctimeetingtech.com/esmo2022/attendee/confcal/show/session/152
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03055013
Allaf, M. (2022). LBA67 – Phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients (Pts) with renal cell carcinoma (RCC) undergoing nephrectomy (PROSPER, ECOG-ACRIN EA8143), a National Clinical Trials Network trial. ESMO Congress 2022 – Conference Calendar.
