Cediranib (VEGFR TKI) + weekly paclitaxel lifts early disease control/ORR in platinum-pretreated endometrial cancer—but benefit washes out by 6 months

Cediranib is an oral VEGFR1-3–targeting anti-angiogenic TKI; in COPELIA (UK multicentre, open-label, randomized Phase 2; NCT03570437), patients with advanced/recurrent endometrial cancer after ≥1 prior platinum regimen received weekly paclitaxel alone (n=41), cediranib+weekly paclitaxel (n=41), or cediranib+olaparib (PARP inhibitor; n=42). Cediranib+paclitaxel improved 3‑month PFS rate (73.2% vs 48.8%; aOR 3.2; p=0.01) and RECIST response (56.4% vs 28.2%; aOR 5.7; p<0.001), but there was no separation at 6 months and no improvement in median PFS; OS was numerically longer but not significant (mOS 18.1 vs 12.8 months; p=0.42)—notably, in the modern post-platinum setting, lenvatinib+pembrolizumab delivers median PFS ~6.7 months and ORR ~32% (pMMR) vs chemo (including weekly paclitaxel) median PFS ~3.8 months and ORR ~15%. Grade 3+ AEs with cediranib+paclitaxel included hypertension (15%), neutropenia (12%), and diarrhea (10%), with QoL worse for GI symptoms; exploratory biomarker work suggested a Tie2 “vascular response” predicted better PFS on cediranib (HR 0.54; p=0.014).