Tisotumab Vedotin Safety and Tolerability in Clinical Practice: Managing Adverse Events

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TL;DR

Tisotumab vedotin, an antibody-drug conjugate for recurrent or metastatic cervical cancer, has a manageable safety profile with key adverse events including ocular toxicity, peripheral neuropathy, and bleeding. Ocular events (60% incidence) can be mitigated through a required eye care plan involving ophthalmology exams, eye drops, and cold packs, while peripheral neuropathy (42% incidence) and bleeding (62% incidence) are managed with dose modifications and supportive care. A comprehensive care team including oncologists and ophthalmologists is essential for early detection and management to optimize treatment adherence and patient outcomes.

Full summary

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**Background:** Tisotumab vedotin-tftv (Tivdak) is a tissue factor-directed antibody-drug conjugate approved for adult patients with recurrent or metastatic cervical cancer (r/mCC) after chemotherapy. The pivotal phase II innovaTV 204 trial demonstrated clinically meaningful responses with a manageable safety profile. Key adverse events (AEs) of interest include ocular AEs, peripheral neuropathy, and bleeding, which require proactive management by a comprehensive care team including oncologists, advanced practice providers, and ophthalmologists.

**Methods:** This narrative review summarizes safety data from the innovaTV 204 trial (NCT03438396) and provides practical recommendations for AE management. The trial enrolled 101 patients (median age 50 years) who received tisotumab vedotin 2 mg/kg (max 200 mg) intravenously every 3 weeks. Patients had received one (70%) or two (30%) prior lines of systemic therapy; 63% had prior bevacizumab plus doublet chemotherapy. The objective response rate was 24% (95% CI 16%–33%), median duration of response 8.3 months, median progression-free survival 4.2 months, and median overall survival 12.1 months. Most AEs were mild to moderate; 92% experienced any-grade treatment-related AEs (TRAEs), 28% had grade ≥3 TRAEs, and 13% had serious TRAEs (one fatal).

**Key Results:** Ocular AEs occurred in 60% of patients across trials; in innovaTV 204, 53% had ocular TRAEs (25% grade 1, 27% grade 2, 2% grade 3). Common events included conjunctivitis (26%), dry eye (23%), and keratitis (11%). Median time to first ocular event was 1.4 months; median resolution time was 0.7 months. Implementation of an eye care plan (baseline and pre-dose ophthalmic exams, corticosteroid and vasoconstrictor eye drops, cold packs, avoidance of contact lenses) reduced ocular event incidence from 80% to 60% in the phase I trial. Peripheral neuropathy occurred in 42% of patients; in innovaTV 204, 33% had peripheral neuropathy TRAEs (17% grade 1, 9% grade 2, 7% grade 3). Median time to onset was 3.1 months; median resolution time was 0.6 months. Bleeding events occurred in 62% of patients; in innovaTV 204, 39% had bleeding TRAEs (34% grade 1, 3% grade 2, 2% grade 3). Most common was epistaxis (30%). Median time to first bleeding event was 0.3 months; median resolution time was 0.5 months. Dose modification guidelines are provided for keratitis, conjunctival ulceration, conjunctivitis, peripheral neuropathy, hemorrhage, and pneumonitis, with dose reductions to 1.3 mg/kg and 0.9 mg/kg.

**Clinical Implications:** A comprehensive care team including ophthalmologists is critical for managing ocular AEs, which may be unfamiliar to gynecologic oncology practitioners. Adherence to the premedication and required eye care plan, along with early referral to ophthalmologists, can mitigate ocular toxicity. Peripheral neuropathy requires baseline assessment, patient education, and dose modifications; nonpharmacologic and pharmacologic interventions (e.g., duloxetine, gabapentin) may alleviate symptoms. Bleeding events are generally low-grade and self-limiting; standard interventions suffice. Patient education on symptom reporting and proactive monitoring are essential to limit treatment-related toxicity and maximize adherence. Ongoing studies (e.g., phase III NCT04697628) will further characterize the safety profile.