datopotamab deruxtecan

DA-toe-POE-tah-mab DER-ux-TEE-kan

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, enzyme inhibitors

High Alert

Unresectable or metastatic, hormone receptor positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer in patients who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.

Datopotamab deruxtecan is an antibody-drug conjugate consisting of datopotamab, a monoclonal antibody directed against Trop-2 (expressed on cancer cells), and DXd, a topoisomerase I inhibitor. After binding to Trop-2, datopotamab deruxtecan is internalized and releases DXd, which then leads to DNA damage and apoptosis.

Therapeutic effects:

Improved progression-free survival.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to extravascular tissues.

Metabolism/Excretion: Datapotamab is degraded into small peptides and amino acids via catabolic pathways; DXd is primarily metabolized by the CYP3A4 isoenzyme. Excretion pathway not characterized.

Half-Life: Datapotamab deruxtecan: 4.8 days; DXd: 5.5 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	unknown

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Mild or moderate renal impairment (CCr 30–<90 mL/min) (↑ risk of interstitial lung disease (ILD)/pneumonitis);
Moderate hepatic impairment (total bilirubin >1.5–3 times upper limit of normal and any AST);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Derm: alopecia, rash, dry skin, hyperpigmentation, pruritus

EENT: dry eye, keratitis, ↑lacrimation, blepharitis, blurred vision, conjunctivitis, meibomian gland dysfunction, photophobia, visual impairment

F and E: hypocalcemia

GI: ↓appetite, ↑liver enzymes, abdominal pain, constipation, diarrhea, nausea, stomatitis, vomiting, dry mouth

GU: ↓fertility

Hemat: anemia, leukopenia, lymphopenia, neutropenia

Neuro: cough, fatigue, headache

Resp: ILD/PNEUMONITIS

Misc: infusion-related reactions

Drug-drug:

None reported.

IV (Adults ≥90 kg): 540 mg every 3 wk; continue until disease progression or unacceptable toxicity.
IV (Adults <90 kg): 6 mg/kg every 3 wk; continue until disease progression or unacceptable toxicity.

Lyophilized powder for injection: 100 mg/vial

Conduct an ophthalmic exam, including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at initiation annually, at end of treatment, and as clinically indicated. Monitor for ocular adverse reactions, including dry eye, keratitis, blepharitis, meibomian gland dysfunction, ↑ lacrimation, conjunctivitis, and blurred vision. Refer patient to ophthalmologist if symptoms occur. If corneal ulcer or stromal opacity occurs or if best corrected distance visual acuity ≤20/200: Hold datopotamab deruxtecan until improved or resolved; then restart at ↓ dose level. If corneal perforation occurs: Permanently discontinue datopotamab deruxtecan. If confluent superficial keratitis, cornea epithelial defect, or ≥3-line loss in best corrected visual acuity occurs: Hold datopotamab deruxtecan until improved or resolved; then restart at the same dose level or consider dose ↓. If nonconfluent superficial keratitis occurs: Continue at current dose. See Dosage Modification for Adverse Reactions below.
Monitor lung status for signs/symptoms of ILD/pneumonitis (dyspnea, cough, hypoxia, fever). CT scan or chest x-ray can confirm. If asymptomatic ILD/pneumonitis occurs: Hold datopotamab deruxtecan until completely resolved and consider corticosteroids. If completely resolved in ≤28 days, maintain current dose; if completely resolved in >28 days, then restart at ↓ dose level. If symptomatic ILD/pneumonitis occurs: Permanently discontinue datopotamab deruxtecan; administer corticosteroids (continue for ≥14 days followed by gradual taper for ≥4 wk). See Dosage Modification for Adverse Reactions below.
Monitor for signs/symptoms of infusion-related reactions (fever, chills, sweating, myalgia, headache, dizziness, nausea, vomiting, urticaria, pruritus, shortness of breath, wheezing ) during and within 1 hr of infusion. Premedication should be given with each infusion unless clinically indicated otherwise (acetaminophen, antihistamines, antiemetic, steroid, IV fluids, and/or oxygen therapy). May ↓ observation time to 30 min if 2nd infusion tolerated. If Grade 1 infusion-related reactions occur:↓ infusion rate by 50%. If Grade 2 infusion-related reactions occur: Hold datopotamab deruxtecan and administer supportive care medications; if improves to Grade ≤1, restart and ↓infusion rate by 50% and administer all subsequent infusions at the ↓ rate. If Grade 3 or 4 infusion-related reactions occur: Permanently discontinue datopotamab deruxtecan.
Monitor for stomatitis, including oral ulcers and mucositis. If Grade 1 stomatitis occurs: Optimize prophylactic treatment and supportive medications; continue at current dose. If Grade 2 stomatitis occurs: Hold datopotamab deruxtecan until resolved to Grade ≤1; restart at same dose level for 1st occurrence; if recurrent, consider restarting at ↓ dose. If Grade 3 stomatitis occurs: Hold datopotamab deruxtecan until resolved to Grade ≤1; restart at ↓ dose. If Grade 4 stomatitis occurs: Permanently discontinue datopotamab deruxtecan. See Dosage Modification for Adverse Reactions below.

Lab Test Considerations:

Verify pregnancy status when starting therapy and monitor regularly.
Treat patients based on presence of EGFR mutation status in tumor or plasma specimens assessed at any time from initial diagnosis; does not need to be repeated once EGFR status has been established.

Administer in a setting where cardiopulmonary resuscitation medication and equipment are available.
Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion.
Concurrent Medications: Administer preservative-free lubricant eye drops 4 times daily and as needed and steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL) 4 times daily and as needed.
Premedications: Diphenhydramine 25–50 mg IV/PO and acetaminophen 650–1000 mg IV/PO 30–60 min prior to each infusion; antiemetics (5-HT₃ receptor antagonist or appropriate alternatives) IV/PO prior to each infusion as needed with or without corticosteroids.
Dosage Modification for Adverse Reactions: Do not re-escalate datopotamab deruxtecan following a dose ↓. 1st dose reduction: 4 mg/kg (max = 360 mg for patients ≥90 kg). 2nd dose ↓: 3 mg/kg (max = 270 mg for patients ≥90 kg). 3rd dose reduction: Permanently discontinue datopotamab deruxtecan.
Missed or Delayed Dose: If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle. Adjust the schedule of administration to maintain a 3 wk interval between doses.

IV Administration:

Do not administer as an IV push or bolus.
Y-Site Compatibility:
- Do not administer other drugs through the same IV line

Explain purpose and side effects of datopotamab deruxtecan. Do not stop receiving drug without consulting health care provider. If an appointment is missed, contact health care provider as soon as possible to reschedule. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic eye exams will be needed.
May cause temporary blurred vision. Warn patient to avoid driving or other activities requiring clear vision until response to medication is known or until blurred vision resolves. Avoid use of contact lenses unless directed by eye care provider.
Instruct patient to notify health care provider or call 911 immediately to seek medical care if swelling of face, eyes, lips, or tongue or if difficulty swallowing or breathing occur.
Advise patient to report symptoms of ILD/pneumonitis (cough, shortness of breath, fever, other new or worsening respiratory symptoms).
Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to use sponge brush and to rinse mouth with water after eating and drinking. Topical therapy may be used if mouth pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and not to breastfeed during treatment and for 1 mo after last dose. Advise women of reproductive potential to use effective contraception during treatment and for 7 mo after last dose. Advise men with female partners of reproductive potential to use effective contraception during treatment and for 4 mo after last dose.

Improved progression-free cancer survival.

Datroway

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Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

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Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

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US Brand Names ⬆