LAZERTINIB TAB

Clinical Criteria Summary

First-line therapy for locally advanced or metastatic non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858R substitution mutations
Used in combination with amivantamab

Anticoagulation to prevent VTE during first 4 months of combination therapy
Dermatologic prophylaxis: oral antibiotics for first 12 weeks followed by topical clindamycin, chlorhexidine wash daily, moisturizer, and sunscreen as per package insert
Counseling on treatment risks vs benefits and use of effective contraception during and for 3 months after last treatment of lazertinib plus amivantamab (for females who can become pregnant and males with female partners who can become pregnant)

Goals of care and role of Palliative Care consult have been discussed and documented

First-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations
Indicated specifically in combination with amivantamab
Applicable to adults; eligibility includes asymptomatic or previously treated and stable brain metastases, ECOG performance status 0-1, and adequate organ and bone-marrow function

Lazertinib 240 mg orally once daily with or without food
Administered in combination with amivantamab (IV or SC)
Amivantamab dosing: 1050 mg (or 1400 mg if ≥80 kg) IV weekly for the first 4 weeks, then every 2 weeks

Anticoagulation prophylaxis (excluding Vitamin K antagonists) required for the first 4 months; consider discontinuation if no venous thromboembolism (VTE) occurs in the first 4 months
Doxycycline or minocycline for the first 12 weeks, followed by clindamycin lotion to the scalp for the next 9 months
Daily application of non-comedogenic moisturizer
Daily wash with chlorhexidine 4%
Strict limitation of sun exposure with use of UVA/UVB sunscreen and protective clothing

Monitor for venous thromboembolic events, interstitial lung disease/pneumonia, dermatologic adverse events (rash, dermatitis acneiform, pruritus, dry skin), ocular toxicity (including keratitis), and EF toxicity
Manage dermatologic reactions with topical steroids and/or oral antibiotics; severe reactions require oral steroids and referral to dermatology
Adverse events associated with the combination may limit use in the VA population

NCCN Guidelines list amivantamab plus lazertinib as a preferred option for first-line treatment of non-squamous NSCLC with advanced/metastatic disease and EGFR exon 19 del or exon 21 L858R substitution
VA Clinical Pathway includes the combination as a first-line option alongside osimertinib and osimertinib plus platinum-based chemotherapy (shared decision-making)
FDA review supports use based on progression-free survival improvement, duration of response improvement, and a trend in improved overall survival with a favorable risk-benefit profile