Cosiporfin sodium (DVDMS)-mediated photodynamic therapy (PDT) versus treatment of physician’s choice (TPC) in patients (pts) with advanced esophageal cancer (aEC): a phase III, randomized, open-label, multicenter trial

Challenges persist in the treatment of aEC, especially in pts with esophageal stenosis and dysphagia, worsening nutrition and impeding anti-tumor therapies, leading to poor prognosis. Pts with local recurrence or metastasis EC and Stoller dysphagia grade ≥2 were randomized 2:1 to DVDMS-mediated PDT or TPC. The primary endpoint was esophageal overall response rate (es-ORR). As of November 11, 2024, 186 pts were randomly assigned. The es-ORR was 51.6% with DVDMS-PDT vs 8.1% with TPC at day 28 (P<0.0001). At a median follow-up of 8.9 months (mos), the median progression-free survival was 2.8 vs 2.2 mos (HR=0.61, P=0.0244), respectively. Time to progression was 5.9 vs 3.9 mos (HR=0.45, P=0.0056). Median overall survival (OS) was 7.0 vs 6.4 mos (HR=0.88, P=0.5169) and RPSFTM-adjusted median OS was 7.0 vs 4.7 mos (HR=0.64, P=0.0223). Phototoxicity was negative in 64.9% pts in DVDMS-PDT group on day 7, increasing to 91.4% by day 28. Grade ≥3 treatment-emergent adverse events occurred in 38.2% of the DVDMS-PDT group and 49.2% of the TPC group. DVDMS-PDT significantly improved esophageal stenosis and dysphagia compared to TPC in pts with aEC, with prolonged PFS and TTP, potential better OS and a manageable safety profile.