Adjuvant P is the standard of care for pts with intermediate-high/high risk of relapse after nephrectomy (Nx), as well as for those with M1NED within 1y of previous Nx. Although omRCC pts may receive anti-PD-1-based combos, the optimal management of those eligible for MDT remains uncertain.
The PE-PE trial (NCT05578664) is a randomized, open-label, multicenter phase II study evaluating the efficacy of P in delaying tumor progression for omRCC pts candidates for MDT, including surgery or SABR to all metastatic sites. Eligible pts had undergone prior Nx and presented with ≤3 metastases within 5 years of Nx or previous metastasectomy. Pts were randomized 2:1 to receive P 400 mg every 6 weeks for 9 cycles (1 year) plus MDT (P+MDT) or MDT alone. The first dose of P was administered before MDT. The primary endpoint was relapse-free survival (RFS), while others included distant RFS, local relapse, OS, and safety.
85 pts were randomized between March 2023 and February 2026: 56 to the P+MDT arm and 29 to the MDT-alone arm. Baseline characteristics were well balanced between treatment groups. SABR was selected in 73% vs. 72% of pts, while surgery was performed in 23% vs. 28%, respectively. The median number of P cycles administered was 6.6. The most frequent reasons for P discontinuation were disease progression (11 pts) and adverse events (AE, 4 pts). After a median follow-up of 17.5 mos, 35 RFS events were observed (19 vs.16), with two deaths (one in each arm). Median RFS was 25.4 mos in the P+MDT arm vs. 11.0 mos in the MDT-alone arm (HR 0.47; 95% CI, 0.24-0.92; p=0.024). Regarding safety, 80% vs. 21% of pts experienced at least one AE, while G3 AEs occurred in 7% vs. 3% of pts in the P+MDT and MDT-alone arms, respectively. P-related AEs of any G occurred in 59%, the most common being hypothyroidism (23%), fatigue (18%), and diarrhea (16%). Two pts experienced G3 toxicity without G4 or 5.
The PE-PE trial supports the use of 1 year of perioperative P in pts with omRCC eligible for MDT, demonstrating a statistically significant and clinically meaningful improvement in RFS with a manageable and consistent safety profile.
NCT05578664.
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