Background
ALIENOR (ENGOT-ov7) was an academic, international, open-label, randomized phase II trial using an adaptive Bayesian design to evaluate whether adding bevacizumab to weekly paclitaxel improves outcomes in women with relapsed ovarian sex cord-stromal tumors (SCSTs) — a rare group of ovarian neoplasms (predominantly granulosa cell tumors) with no established standard treatment after platinum failure. It is the first randomized trial conducted in this rare tumor type.
Interventions and follow up
Arm A: Paclitaxel 80 mg/m² IV days 1, 8, 15 every 28 days (single-agent, 6 cycles)
Arm B: Paclitaxel 80 mg/m² IV days 1, 8, 15 every 28 days + bevacizumab 10 mg/kg q2w (6 cycles) → bevacizumab 15 mg/kg q3w maintenance ×1 year
Population: n=60 (32 paclitaxel alone, 28 paclitaxel + bevacizumab); 28 centers in France, Germany, Italy, Japan, Belgium; crossover to bevacizumab permitted after progression
Primary endpoint: 6-month progression-free rate (Bayesian adaptive design)
mFollow-up: 38.9 months
Arm B: Paclitaxel 80 mg/m² IV days 1, 8, 15 every 28 days + bevacizumab 10 mg/kg q2w (6 cycles) → bevacizumab 15 mg/kg q3w maintenance ×1 year
Population: n=60 (32 paclitaxel alone, 28 paclitaxel + bevacizumab); 28 centers in France, Germany, Italy, Japan, Belgium; crossover to bevacizumab permitted after progression
Primary endpoint: 6-month progression-free rate (Bayesian adaptive design)
mFollow-up: 38.9 months
Results
6-mo PFS rate: 71% (95% credible interval 55–84%) paclitaxel alone vs 72% (55–87%) paclitaxel + bevacizumab; Bayesian P[bev > pac] = 57%, below the pre-specified superiority threshold of 90%
ORR: 25% (paclitaxel) vs 44% (paclitaxel + bevacizumab)
Primary endpoint: bevacizumab did not significantly improve the 6-mo PFS rate
ORR: 25% (paclitaxel) vs 44% (paclitaxel + bevacizumab)
Primary endpoint: bevacizumab did not significantly improve the 6-mo PFS rate
Adverse events
Overall: Grade ≥3 toxicity generally manageable in both arms; only 1 patient discontinued combination within 6 months due to toxicity
Bevacizumab-related: hypertension and proteinuria as expected; overall toxicity acceptable for this rare tumor population
Bevacizumab-related: hypertension and proteinuria as expected; overall toxicity acceptable for this rare tumor population
Conclusions
Bevacizumab added to weekly paclitaxel does not improve the 6-month PFS rate beyond paclitaxel alone in relapsed sex cord-stromal tumors (Bayesian probability of superiority 57%), but weekly paclitaxel achieves a clinically meaningful 6-month PFS rate of 71%, establishing weekly paclitaxel as a standard-of-care option after platinum failure in this rare tumor type.
Key Limitations
Small sample size (n=60) limits power to detect subgroup differences; Bayesian adaptive design provides probability estimates rather than traditional P-values, limiting conventional statistical interpretation; predominantly granulosa cell tumors (other SCSTs underrepresented); bevacizumab crossover from the control arm after progression partially confounds long-term outcomes; no molecular biomarker selection (FOXL2 C402G, inhibin); no chemotherapy-free hormonal comparator arm; phase II only — no OS endpoint.
Clinical Context
ALIENOR is landmark as the first randomized trial in ovarian SCSTs, providing Level I evidence for weekly paclitaxel in this rare entity previously managed anecdotally. The study established weekly paclitaxel as standard in GINECO/ENGOT recommendations. The numerically higher ORR with bevacizumab (44% vs 25%) did not translate to a primary endpoint improvement, possibly due to sample size. Ongoing investigations target FOXL2 mutation, the inhibin pathway, and CDK4/6 inhibition in granulosa cell tumors. ALIENOR's Bayesian design is a model for future rare-tumor trials where conventional phase III enrollment is impractical.