PErioperative PEmbrolizumab (P) plus metastasis-directed therapy (MDT) versus MDT alone in patients (pts) with oligometastatic renal cell carcinoma (omRCC): The randomized phase II PE-PE trial

PE-PE

Paziente / Popolazione Intervento / Esposizione Confronto Esito

In patients with oligometastatic renal cell carcinoma eligible for metastasis-directed therapy, perioperative pembrolizumab plus metastasis-directed therapy improved relapse-free survival compared with metastasis-directed therapy alone.

N

85pazienti

Disegno

Randomised, open-label, multicentre phase II trial (NCT05578664) in which patients with oligometastatic renal cell carcinoma, prior nephrectomy and up to 3 metastases within 5 years of nephrectomy or previous metastasectomy, who were candidates for metastasis-directed therapy (surgery or SABR to all metastatic sites), were randomised 2:1 to 1 year of perioperative pembrolizumab plus metastasis-directed therapy or metastasis-directed therapy alone.

Esito

Relapse-free survival.

RisultatoMedian relapse-free survival 25.4 months with pembrolizumab plus metastasis-directed therapy vs 11.0 months with metastasis-directed therapy alone (HR 0.47; 95% CI 0.24-0.92; P = 0.024), after a median follow-up of 17.5 months and 35 RFS events (19 vs 16). Two deaths occurred, one in each arm. Any adverse event 80% vs 21%. Grade 3 adverse events 7% vs 3%. Pembrolizumab-related adverse events of any grade occurred in 59%, most often hypothyroidism (23%), fatigue (18%) and diarrhoea (16%), with no grade 4 or 5 toxicity.

Iacovelli R, Volta AD, Bimbatti D, et al. Presented at ESMO Congress 2026, abstract LBA88, 25 October. Not yet published.

Discussione e critica

This small randomised phase II trial shows that adding perioperative pembrolizumab to metastasis-directed therapy roughly doubled median relapse-free survival in oligometastatic renal cell carcinoma. With a median follow-up of 17.5 months, 35 events and only two deaths, overall survival cannot yet be assessed. Relapse-free survival is a surrogate endpoint, the design was open label, and the 2:1 allocation left only 29 patients in the control arm. The abstract gives no results for distant relapse-free survival or local relapse, and patients received a median of 6.6 of the planned 9 cycles, with stopping for progression or adverse events.