Background
Phase 3, multinational, open-label. N=502 recurrent or metastatic cervical cancer with progression after first-line combination therapy (second- or third-line setting). Tisotumab vedotin: tissue-factor-directed ADC delivering MMAE.
Results
Interventions and follow up: Arm A: tisotumab vedotin 2.0 mg/kg IV q3wk until progression/toxicity (n=253).
Arm B: investigator's-choice chemotherapy — topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed (n=249).
Randomization: 1:1.
Primary endpoint: overall survival.
mFollow up: NR.
Results: OS: 11.5 vs 9.5 mo, HR 0.70, 95% CI 0.54–0.89, P=.004 (30% lower risk of death).
PFS: 4.2 vs 2.9 mo, HR 0.67, 95% CI 0.54–0.82, P<.001.
Confirmed ORR: 17.8% vs 5.2%, OR 4.0, 95% CI 2.1–7.6, P<.001.
Arm B: investigator's-choice chemotherapy — topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed (n=249).
Randomization: 1:1.
Primary endpoint: overall survival.
mFollow up: NR.
Results: OS: 11.5 vs 9.5 mo, HR 0.70, 95% CI 0.54–0.89, P=.004 (30% lower risk of death).
PFS: 4.2 vs 2.9 mo, HR 0.67, 95% CI 0.54–0.82, P<.001.
Confirmed ORR: 17.8% vs 5.2%, OR 4.0, 95% CI 2.1–7.6, P<.001.
Adverse events
Overall: any AE 98.4% vs 99.2%; G3+ AEs 52.0% vs 62.3%.
Characteristic (tisotumab vedotin): ocular events (conjunctivitis, keratitis), peripheral neuropathy, bleeding (epistaxis).
Discontinuation for toxicity: 14.8% (tisotumab vedotin).
Characteristic (tisotumab vedotin): ocular events (conjunctivitis, keratitis), peripheral neuropathy, bleeding (epistaxis).
Discontinuation for toxicity: 14.8% (tisotumab vedotin).
Conclusions
Tisotumab vedotin improved OS, PFS, and ORR vs chemotherapy in recurrent/metastatic cervical cancer after first-line therapy; first tissue-factor-targeted ADC with an OS benefit in second-line cervical cancer.
Key Limitations
Absolute OS gain modest (2 mo). Open-label design with heterogeneous investigator's-choice chemotherapy introduces potential bias. Distinctive ocular and neuropathy toxicities demand structured prophylaxis and may limit tolerability. Activity after prior checkpoint inhibitors and bevacizumab warrants further definition.
Clinical Context
Confirmed the accelerated-approval signal from single-arm innovaTV 204, supporting full FDA approval (2024) and EMA approval of tisotumab vedotin as second-line therapy. ESMO endorses it for recurrent/metastatic cervical cancer progressing after platinum-based chemotherapy, bevacizumab, and immunotherapy. Ocular prophylaxis required.