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

Patient / Population Intervention / Exposition Comparaison Critère de jugement

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

85patients

Schéma

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.

Critère

Relapse-free survival.

RésultatMedian 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.

Discussion et critique

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.