TISOTUMAB VEDOTIN-TFTV INJ,LYPHL

Clinical Criteria Summary

Adults with recurrent or metastatic cervical cancer
Disease progression on or after chemotherapy
Second-line or subsequent therapy following failure of doublet chemotherapy (paclitaxel + cisplatin, carboplatin, or topotecan) plus bevacizumab (if eligible) and pembrolizumab (for PD-L1-positive tumors)
Recurrent setting following prior systemic therapy and prior pembrolizumab per VHA Oncology Cervical Cancer Clinical Pathway

Topical vasoconstrictor drops immediately prior to each infusion
Corticosteroid eye drops TID for 72 hours after each infusion
Cold packs during infusion and frequent lubricating eye drops
Avoid contact lenses for the entire duration of therapy
Ophthalmologic exam prior to initiation, prior to every cycle for 9 cycles, and as clinically indicated (visual acuity, slit lamp anterior eye, eye movement)

Ocular toxicity: May require dose modification; refer new or worsening symptoms to an eye care provider
Pneumonitis: Withhold for persistent or recurrent Grade 2; permanently discontinue for Grade 3 or 4
Peripheral neuropathy: Withhold or reduce doses, or permanently discontinue for Grade 3 or 4
Hemorrhage: Permanently discontinue for pulmonary or CNS hemorrhage; follow prescribing information for other bleeding types
Severe cutaneous adverse reactions (SCAR): Permanently discontinue for confirmed Grade 3 or 4

None stated
Embryo-fetal toxicity: Advise patients of fetal risks; persons of reproductive potential must use effective contraception during treatment and for 2 months after the last dose

Monitor closely with strong CYP3A4 inhibitors due to MMAE being a CYP3A4 substrate

Absolute Neutrophil Count greater than or equal to 1500/mcL unless associated with Duffy-null Associated Neutrophil Count (DANC)
Platelet count greater than or equal to 100,000/mcL
Clinically significant cardiovascular disease (including unstable angina or acute MI within 6 months; CHF NYHA grade III/IV; reduced EF < 45%; prolonged QTc interval)
Active or uncontrolled infection
Clinically significant bleeding risk (coagulation defects, diffuse alveolar hemorrhage from vasculitis, known bleeding diathesis, ongoing major bleeding, trauma with increased risk of life-threatening bleeding, severe head trauma or intracranial surgery within past 8 weeks)
History of intracerebral arteriovenous malformation, cerebral aneurysm or stroke
Active ocular surface disease or high-risk for cicatrizing conjunctivitis (e.g. Wagner syndrome, atopic keratoconjunctivitis, autoimmune disease affecting eyes), ocular Stevens-Johnson syndrome, mucus pemphigoid or penetrating ocular transplant
Peripheral neuropathy greater than or equal to grade 2
Moderate or severe hepatic impairment (AST greater than 3 times upper limit of normal or total bilirubin greater than 1.5 times the upper limit of normal)
Severe renal impairment (CrCl 15 to less than 30 ml/min) or end-stage renal disease
Unmanageable drug-drug interaction identified
Prior treatment with monomethyl auristatin E (MMAE)-containing drugs
Pregnancy
Lactating

Diagnosis of cervical cancer (squamous cell, adenocarcinoma or adenosquamous histology)
Disease progression on or after at least one prior chemotherapy regimen for recurrent or metastatic disease and bevacizumab, if eligible, and pembrolizumab, if eligible

Care provided by a VA/VA Community Care hematology/oncology provider
Goals of care and role of Palliative Care consult have been discussed and documented
Eastern Cooperative Oncology Group Performance Status 0-1
Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 2 months after stopping treatment (4 months for male patients with female partners) for patients who can become pregnant and patients with partners who can become pregnant
Advising patients not to breastfeed during treatment and for at least 1 week after the last dose
Advising patients NOT to wear contact lenses throughout the course of therapy