Tisotumab vedotin-tftv, a tissue factor (TF)-directed immune globulin (Ig) G1-kappa antibody conjugated with the microtubule inhibitor monomethyl auristatin E (MMAE), is an antineoplastic agent.1
Tisotumab vedotin-tftv is used for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.1, 2, 3, 4, 5
The efficacy of tisotumab vedotin was evaluated in the innovaTV 301 study, which was an open-label, active-controlled, multicenter, randomized trial.1 The study included 502 patients with recurrent or metastatic cervical cancer who had previously received 1 or 2 systemic treatments, including chemotherapy, with or without bevacizumab, and/or an anti-programmed death ligand 1 (anti-PD-L1) drug.1, 3 Tisotumab vedotin therapy resulted in significantly longer median overall survival and progression-free survival compared to chemotherapy, along with a higher confirmed objective response rate, substantially reducing the risk of death and disease progression in patients with recurrent or metastatic cervical cancer.1, 3
In the innovaTV 301 study, patients were randomly assigned to receive either tisotumab vedotin-tftv (2 mg/kg by IV infusion every 3 weeks) or the investigator's choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) until unacceptable toxicity or disease progression occurred.1, 3 The primary efficacy measure was overall survival, defined as the time from randomization to death from any cause.1, 3 The median age of patients was 50 years (range: 26 to 80 years); 49% were White and 36% were Asian.1, 3 The baseline Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 54% of patients and 1 in 46% of patients.1, 3 Among the study participants, 63% had squamous cell carcinoma, 90% had extrapelvic disease, and almost all patients had received one (61%) or two (38%) prior lines of systemic therapy, including chemotherapy that included bevacizumab (64%), and anti-PD-1 or anti-PD-L1 therapy (27%).1, 3 Patients receiving tisotumab vedotin-tftv showed significantly prolonged overall survival (11.5 versus 9.5 months), progression-free survival (4.2 versus 2.9 months) and objective response rate (17.8 versus 5.2%) compared to patients receiving chemotherapy. 1, 3
Efficacy of tisotumab vedotin-tftv was also evaluated in an open-label, multicenter, single-arm, phase 2 trial (innovaTV 204) in 101 patients with recurrent or metastatic cervical cancer who received no more than 2 prior systemic treatments, including one prior platinum-based chemotherapy regimen.1, 5 Patients received tisotumab vedotin-tftv (2 mg/kg by IV infusion every 3 weeks) until disease progression or unacceptable toxicity occurred.1, 5 Results of the study demonstrated clinically meaningful antitumor activity with tisotumab vedotin in patients with recurrent or metastatic cervical cancer following first-line treatment.1, 5 The confirmed objective response rate as assessed by an independent review committee (IRC) according to RECIST v1.1 criteria was 24%.1, 5 Median duration of response was 8.3 months.1, 5
Treatment of recurrent or metastatic cervical cancer typically includes first-line systemic treatment with bevacizumab and chemotherapy (or pembrolizumab and chemotherapy with or without bevacizumab in eligible patients).4, 6, 7 Patients with disease progression on first-line therapy have limited treatment options; available therapies in this setting include single agent chemotherapies.4, 7 Tisotumab vedotin provides another treatment option for patients with recurrent or metastatic cervical cancer.4
Dispensing and Administration Precautions
Advise patients to avoid wearing contact lenses for the entire duration of therapy unless advised by their eye care provider.1
Tisotumab vedotin-tftv is administered by IV infusion only; do not administer as an IV push or bolus.1 The drug is commercially available as a lyophilized powder that must be reconstituted and diluted prior to administration.1
Tisotumab vedotin infusion is administered over 30 minutes through an IV line containing a 0.2 µm inline filter.1
Because the drug can cause severe ocular toxicities, clinicians must adhere to the required premedication and eye care recommendations before, during, and after infusion.1
Do not mix with or administer as an infusion with any other medications.1
To reconstitute the lyophilized powder, first calculate the dose based on the patient's weight to determine the number of vials needed.1 Reconstitute each 40-mg vial with 4 mL of sterile water for injection to achieve a concentration of 10 mg/mL.1 Gently swirl the vials until the drug is fully dissolved, then allow the contents to settle; do not shake or expose the vial to direct sunlight.1 Inspect the reconstituted solution for clarity, ensuring it is clear to slightly opalescent, colorless to brownish-yellow, and free of particles; discard the vial if discoloration or particulate matter is observed.1 If not used immediately, the reconstituted vials may be stored in the refrigerator (2 to 8°C) for up to 24 hours or at room temperature (up to 25°C) for a maximum of 8 hours before dilution; do not freeze.1
Withdraw the calculated amount of reconstituted solution from the vial(s) and transfer into an infusion bag, then dilute with 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection to achieve a final concentration of 0.7 to 2.4 mg/mL.1 Gently mix by inverting the bag without shaking, and avoid exposure to direct sunlight.1 Inspect the infusion bag for particulate matter or discoloration; discard if any is observed.1 Dispose of any unused solution left in the single-dose vials.1 If not used immediately, the diluted solution may be stored in the refrigerator (2-8°C) for up to 24 hours if prepared with 5% dextrose injection, for up to 18 hours if prepared with 0.9% sodium chloride injection, or for up to 12 hours if prepared with lactated Ringer's injection.1 The solution should be discarded if the storage time exceeds these limits.1 Once removed from refrigeration, complete administration of the diluted infusion solution within 4 hours (including infusion time).1
Administer the tisotumab vedotin infusion over 30 minutes.1
The recommended adult dosage of tisotumab vedotin-tftv is 2 mg/kg (up to a maximum of 200 mg for patients weighing ≥100 kg) administered as an IV infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity occurs.1
Dosage Adjustments for Adverse Reactions
If an adverse reaction occurs, treatment interruption, dosage reduction, and/or discontinuance of therapy may be necessary based on type and severity of the adverse effect.1
The manufacturer's recommended dosage reduction schedule and dosing modifications for adverse reactions are provided in Tables 1 and 2.1
For ocular adverse reactions (keratitis; conjunctival or corneal scarring or symblepharon; conjunctivitis and other ocular adverse reactions), refer patients to an eye care provider promptly for an assessment of new or worsening ocular symptoms.1
Tisotumab Vedotin-tftv Dose Level | |
|---|---|
Starting dose | 2 mg/kg (up to a maximum of 200 mg for patients ≥100 kg).1 |
First dose reduction | 1.3 mg/kg (up to a maximum of 130 mg for patients ≥100 kg).1 |
Second dose reduction | 0.9 mg/kg (up to a maximum of 90 mg for patients ≥100 kg); permanently discontinue in patients who cannot tolerate 0.9 mg/kg.1 |
Adverse Reaction | Severity, Occurrence, and Recommendation |
|---|---|
Keratitis | Nonconfluent superficial keratitis (any occurrence): monitor.1 Confluent superficial keratitis, a corneal epithelial defect, or a 3 line or more loss in best corrected visual acuity (first occurrence): withhold dose until resolution or improvement to nonconfluent superficial keratitis, then resume treatment at the next lower dose level.1 Confluent superficial keratitis, a corneal epithelial defect, or a 3 line or more loss in best corrected visual acuity (second occurrence): permanently discontinue.1 Ulcerative keratitis or perforation (any occurrence): permanently discontinue.1 |
Conjunctival or corneal scarring or symblepharon | Any scarring or symblepharon (any occurrence): permanently discontinue.1 |
Conjunctivitis and other ocular adverse reactions | Nonconfluent superficial punctate conjunctival defects, mild vasodilation (any occurrence): monitor.1 Confluent superficial punctate conjunctival defects, moderate to severe vasodilation (first occurrence): withhold dose until resolution or improvement to nonconfluent superficial punctate conjunctival defects, mild vasodilation, then resume treatment at the same dose.1 Confluent superficial punctate conjunctival defects, moderate to severe vasodilation (second occurrence): withhold dose until resolution or improvement to nonconfluent superficial punctate conjunctival defects, mild vasodilation, then resume treatment at the next lower dose level; if no resolution or improvement to nonconfluent superficial punctate conjunctival defects, mild vasodilation, permanently discontinue.1 Confluent superficial punctate conjunctival defects, moderate to severe vasodilation (third occurrence): permanently discontinue.1 Conjunctival ulcer, conjunctival neovascularization, or fibrovascular scarring (any occurrence): permanently discontinue.1 |
Peripheral neuropathy | Grade 2 (any occurrence, either initial or worsening of pre-existing condition): withhold dose until grade ≤1, then resume treatment at the next lower dose level.1 Grade 3 or 4 (any occurrence): permanently discontinue.1 |
Hemorrhage | Any grade pulmonary or CNS hemorrhage (any occurrence): permanently discontinue.1 Grade 2 in any other location (any occurrence): withhold until resolved, then resume treatment at the same dose.1 Grade 3 in any other location (first occurrence): withhold dose until resolved, then resume treatment at the same dose.1 Grade 3 in any other location (second occurrence): permanently discontinue.1 Grade 4 in any other location (any occurrence): permanently discontinue.1 |
Pneumonitis | Grade 2 (any occurrence): Withhold dose until grade ≤1 for persistent or recurrent pneumonitis, consider resuming treatment at next lower dose level.1 Grade 3 or 4 (any occurrence): permanently discontinue.1 |
Severe cutaneous adverse reactions (including Stevens-Johnson syndrome [SJS]) | Suspected, any grade (any occurrence): immediately withhold dose and consult a specialist to confirm the diagnosis Confirmed grade 3 or 4: permanently discontinue |
Avoid use in patients with moderate or severe hepatic impairment defined as aspartate aminotransferase (AST) >3 times upper limit of normal (ULN) or total bilirubin >1.5 times ULN.1 In patients with mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST), closely monitor for adverse reactions, but no dosage adjustment to the starting dosage is needed.1
Systemic exposure to tisotumab vedotin and MMAE does not appear to be altered in patients with creatinine clearance ≥30 mL/minute.1 However, the manufacturer does not make any recommendations for dosing in patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
A boxed warning on the risk of severe ocular toxicity, which may result in vision changes, severe vision loss, or corneal ulceration, has been included in the prescribing information for tisotumab vedotin-tftv.1
Ocular adverse reactions occurred in 55% of patients with cervical cancer treated with tisotumab vedotin-tftv in clinical trials, with common reactions including conjunctivitis (32%), dry eye (24%), keratopathy (17%), and blepharitis (5%).1 Severe (grade 3) ocular reactions occurred in 3.3% of patients, with 1.2% experiencing severe ulcerative keratitis, including one patient who required corneal transplant.1 Other serious eye conditions (i.e., conjunctival ulcer, corneal erosion, conjunctival erosion, symblepharon) were reported in a small percentage of patients.1 The median onset to first ocular adverse event was 1.2 months, with 59% of patients achieving complete resolution and 31% showing partial improvement.1 Ocular reactions led to permanent discontinuation in 6% of patients. In some cases, delayed ocular reactions occurred more than 30 days after stopping treatment.1
Perform an ophthalmic exam, including visual acuity and slit-lamp examination of the anterior eye segment, before starting treatment, before each cycle for the first 9 cycles, and as clinically needed.1 Strictly follow premedication eye drop protocols and required eye care before, during, and after each infusion.1 Withhold treatment until improvement and then consider resuming therapy, reducing the dose, or discontinuing use based on the severity of the toxicity.1
Other Warnings and Precautions
Peripheral neuropathy occurred in 39% of cervical cancer patients treated with tisotumab vedotin-tftv in clinical trials, with 6% experiencing severe (grade 3) cases.1 Types of neuropathy reported included peripheral sensory neuropathy, paresthesia, and muscular weakness.1 One patient with a different tumor type developed Guillain-Barré syndrome.1 The median time of onset of peripheral neuropathy was 2.4 months.1 Among those affected, 18% had complete resolution, and 21% showed partial improvement.1 Peripheral neuropathy led to tisotumab vedotin discontinuation in 7% of cervical cancer patients.1
Monitor patients for signs and symptoms of neuropathy, such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia.1 For patients experiencing new or worsening peripheral neuropathy, withhold dose, then reduce dose or permanently discontinue tisotumab vedotin based on the severity of peripheral neuropathy.1
Hemorrhage occurred in 51% of cervical cancer patients treated with tisotumab vedotin-tftv, with epistaxis being the most common (33%).1 Severe (grade 3) hemorrhage occurred in 4% of patients.1 The median onset was 0.3 months, with 71% of cases fully resolving and 12% showing partial resolution.1
Monitor patients for signs and symptoms of hemorrhage.1 For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue tisotumab vedotin.1 For grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence.1
Pneumonitis that is severe, potentially life-threatening, or fatal can occur with vedotin-containing antibody-drug conjugates, including tisotumab vedotin.1 In clinical trials with cervical cancer patients, 0.9% experienced pneumonitis, including one fatal case.1
Withhold tisotumab vedotin for patients who develop persistent or recurrent grade 2 pneumonitis and consider dose reduction.1 Permanently discontinue tisotumab vedotin in all patients with grade 3 or 4 pneumonitis.1
Severe Cutaneous Adverse Reactions
Severe cutaneous adverse reactions including life-threatening or fatal Stevens-Johnson syndrome (SJS), can occur with tisotumab vedotin.1 In clinical trials with cervical cancer patients, 1.6% experienced severe cutaneous reactions, with 0.5% being grade 3 or higher, including one fatality.1
If signs or symptoms of severe cutaneous adverse reactions occur, withhold tisotumab vedotin until the etiology of the reaction has been determined.1 Early consultation with a specialist is recommended to ensure greater diagnostic accuracy and appropriate management.1 Permanently discontinue tisotumab vedotin for confirmed grade 3 or 4 severe cutaneous adverse reactions, including SJS.1
Fetal/Neonatal Morbidity and Mortality
Based on the mechanism of action of tisotumab vedotin and findings in animals, the drug can cause fetal harm when administered to a pregnant woman.1 In rats, the small molecule component of tisotumab vedotin (MMAE) caused adverse developmental outcomes, including embryofetal mortality and structural abnormalities, at exposures below those occurring clinically at the recommended dose.1
Advise patients of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with tisotumab vedotin and for 2 months after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment with the drug and for 4 months after the last dose.1
Tisotumab vedotin may cause fetal harm when administered to a pregnant woman based on the mechanism of action and findings from animal studies.1 Human data are not available to assess the drug-associated risk in pregnant women.1 In animal studies, the small molecule component of tisotumab vedotin (MMAE) caused embryofetal death and structural abnormalities in pregnant rats at exposure levels lower than those used clinically.1 MMAE is a synthetic antineoplastic agent that disrupts the microtubule network in cells, leading to cell cycle arrest and apoptosis.1 Patients should be informed of the potential risk to a fetus.1
No data are available on whether tisotumab vedotin is present in human milk or whether the drug has any effects on a breastfed child or on milk production.1 Due to the potential for serious adverse reactions in a breastfed child, lactating women should be advised not to breastfeed during treatment and for 3 weeks after the final dose.1
Females and Males of Reproductive Potential
Tisotumab vedotin can cause fetal harm.1 Before starting treatment, verify pregnancy status in females of reproductive potential.1 Advise females to use effective contraception during treatment and for 2 months after the last dose, and advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.1 Tisotumab vedotin may impair fertility in both females and males, although the effect is reversible in females, based on findings from animal studies with MMAE-containing antibody-drug conjugates.1
Safety and effectiveness of tisotumab vedotin-tftv in pediatric patients have not been established.1
Among the 425 patients with cervical cancer treated with tisotumab vedotin-tftv in clinical trials, 14% were 65 years of age and older, and 2.4% were older than 75 years of age.1 Grade 3 or higher adverse reactions occurred in 60% of patients 65 years of age and older, compared to 55% of those younger than 65 years of age.1 The drug was discontinued due to adverse reactions in 25% of patients 65 years of age and older, versus 13% of those younger than 65 years.1 The clinical studies did not include enough patients 65 years of age and older to determine if they respond differently from those younger than 65 years of age.1
Avoid use in patients with moderate or severe hepatic impairment, defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN.1 In patients with mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin >1 to 1.5 times the ULN and any AST), closely monitor for adverse reactions, but no dosage adjustment to the starting dose is needed.1
No significant differences in exposure to tisotumab vedotin and unconjugated MMAE were observed between patients with mild to moderate renal impairment (creatinine clearance 30 to <90 mL/minute) and those with normal renal function.1 However, the effects of severe renal impairment (creatinine clearance 15 to <30 mL/minute) or end-stage renal disease, with or without dialysis, on the pharmacokinetics of these substances are unknown.1
The most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin, peripheral neuropathy, conjunctival adverse reactions, nausea, fatigue, increased AST, epistaxis, alopecia, increased ALT, and hemorrhage.1
No clinical studies evaluating the drug-drug interaction potential of tisotumab vedotin have been conducted.1 To characterize the drug interaction potential of unconjugated MMAE, clinical studies with another antibody drug conjugate (ADC) that contains MMAE are described; similar effects on tisotumab vedotin and unconjugated MMAE exposures are expected with concomitant use of tisotumab vedotin.1
The small molecule component of tisotumab vedotin, MMAE, is a cytochrome P-450 (CYP) 3A4 substrate.1
In vitro studies indicate that MMAE does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6, nor does it induce any major CYP isoenzymes in human hepatocytes.1
MMAE is a substrate of P-glycoprotein (P-gp), but does not inhibit P-gp.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
CYP3A4 substrates: There were no clinically significant differences in the pharmacokinetics of midazolam, a CYP3A4 substrate, when administered concomitantly with another MMAE-containing ADC.1
Strong CYP3A4 inhibitors: Concomitant use of tisotumab vedotin with strong CYP3A4 inhibitors may increase unconjugated MMAE exposure, which may increase the risk of tisotumab vedotin adverse reactions.1 Closely monitor patients for adverse reactions when used concomitantly with strong CYP3A4 inhibitors.1 Concomitant administration of ketoconazole, a strong CYP3A4 inhibitor, with an MMAE-containing ADC increased the peak plasma concentration of unconjugated MMAE by 25% and the AUC by 34%, without affecting ADC exposure.1
Strong CYP3A4 inducers: Concomitant administration of rifampin, a strong CYP3A4 inducer, with an MMAE-containing ADC decreased the peak plasma concentration of unconjugated MMAE by 44% and the AUC by 46%, with no change in ADC exposure.1
Tisotumab vedotin is a tissue factor (TF)-directed antibody drug conjugate (ADC) consisting of a human anti-TF immune globulin (Ig) G1-kappa antibody linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) through a protease-cleavable vc (valine-citrulline) linker.1 Each monoclonal antibody molecule carries an average of 4 MMAE molecules.1 The monoclonal antibody is produced in a mammalian expression system using Chinese hamster ovary cells.1
Tissue factor initiates the extrinsic blood coagulation cascade and is elevated in several solid tumors, including recurrent cervical cancer.1, 3 Based on nonclinical data, the anticancer effects of tisotumab vedotin arise from binding of the ADC to TF-expressing cancer cells, subsequent internalization of the ADC-TF complex, and MMAE release via proteolytic cleava MMAE disrupts microtubules of actively dividing cells, leading to cell cycle arrest and apoptosis.1 Additionally, it promotes antibody-dependent cellular phagocytosis and cytotoxicity in vitro.1
Pharmacokinetics of tisotumab vedotin and unconjugated MMAE were evaluated after a 2 mg/kg dose over a 3-week cycle.1 Tisotumab vedotin concentrations peaked at the end of infusion, while MMAE peaked 2-3 days later.1 Both compounds achieved steady-state concentrations after one cycle without accumulation.1 The distribution of tisotumab vedotin was moderate, with MMAE showing a significant level of plasma protein binding.1 The median elimination half-lives of tisotumab vedotin and unconjugated MMAE were 4.04 and 2.56 days, respectively, with different rates of clearance.1 Tisotumab vedotin undergoes breakdown into smaller components, including MMAE, which is mainly metabolized by cytochrome P-450 (CYP) 3A4.1 MMAE is expected to be excreted primarily through feces and urine.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV infusion only | 40 mg | Tivdak® | Seagen |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions November 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Seagen Inc. TIVDAK® (tisotumab vedotin) for injection, prescribing information. Bothell, WA; 2024 Apr.
2. de Bono JS, Concin N, Hong DS et al. Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Mar;20(3):383-393. doi: 10.1016/S1470-2045(18)30859-3. Epub 2019 Feb 8. Erratum in: Lancet Oncol. 2019 Dec;20(12):e663. doi: 10.1016/S1470-2045(19)30753-3. PMID: 30745090.
3. Vergote I, González-Martín A, Fujiwara K, et al. Tisotumab Vedotin as second- or third-line therapy for recurrent cervical cancer. N Engl J Med. 2024;391(1):44-55. doi:10.1056/NEJMoa2313811
4. US Food and Drug Administration. Center for Drug Evaluation and Research. Application Number: 761208Orig1s000.Multi-discipline Review. From FDA website [Web]
5. Coleman RL, Lorusso D, Gennigens C et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 May;22(5):609-619. doi: 10.1016/S1470-2045(21)00056-5. Epub 2021 Apr 9. PMID: 33845034.E
6. Chuang LT, Temin S, Berek JS; Management and Care of Patients with Invasive Cervical Cancer Resource-Stratified Guideline Expert Panel. Management and Care of Patients With Invasive Cervical Cancer: ASCO Resource-Stratified Guideline Rapid Recommendation Update. JCO Glob Oncol. 2022 Mar;8:e2200027. doi: 10.1200/GO.22.00027. PMID: 35245079; PMCID: PMC8920468.
7. Chuang LT, Temin S, Camacho R et al. Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline. J Glob Oncol. 2016 May 25;2(5):311-340. doi: 10.1200/JGO.2016.003954. PMID: 28717717; PMCID: PMC5493265.