Does lorlatinib (crizotinib derivative) cause hair loss (alopecia)?

Lorlatinib and Hair Loss

Lorlatinib rarely causes hair loss (alopecia), with an incidence of approximately 6% according to clinical guidelines. 1

Incidence and Characteristics

Lorlatinib, a third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI), has a distinct side effect profile compared to other TKIs. While it can cause several notable adverse effects, hair loss is not among its most common side effects:

• Hair loss (alopecia) occurs in only about 6% of patients taking lorlatinib 1
• This is significantly less frequent than its primary adverse effects, which include:
  • Hypercholesterolemia (82.4%)
  • Hypertriglyceridemia (60.7%)
  • Edema (51.2%)
  • Peripheral neuropathy (43.7%)
  • Central nervous system effects (39.7%) 2

Comparison with Other TKIs

Different TKIs have varying propensities for causing hair-related adverse effects:

• Nilotinib: Rarely causes alopecia (6%) 1
• Dasatinib: Can cause rash (11-33%) but alopecia is not prominently reported 1
• Bosutinib: Associated with rash (20-43%) but not specifically with significant hair loss 1

Management of Lorlatinib-Associated Hair Loss

If hair loss occurs while taking lorlatinib:

1. Assess severity and impact on quality of life

   • Determine if it's grade 1 (mild) or grade 2 (moderate to severe, noticeable to others)
   • Evaluate psychological impact on the patient

2. Consider continuation of therapy

   • Given the low incidence and typically mild nature of lorlatinib-associated hair loss, discontinuation is rarely necessary
   • The benefits of lorlatinib in ALK-positive NSCLC (particularly its efficacy against brain metastases with 71% complete intracranial response) typically outweigh this side effect 3

3. Supportive care measures

   • Gentle hair care practices
   • Avoid harsh chemical treatments
   • Consider consultation with a dermatologist if hair loss is significant

Clinical Context and Importance

When treating ALK-positive NSCLC patients with lorlatinib, clinicians should:

• Focus monitoring on more common and potentially serious adverse effects:

  • Hyperlipidemia (requires regular lipid panel monitoring)
  • Cognitive effects (memory impairment, confusion)
  • Weight gain
  • Peripheral neuropathy 3

• Recognize that hair loss is a relatively minor concern with lorlatinib compared to other anticancer agents like traditional chemotherapy, where alopecia can affect up to 65% of patients 1

Key Takeaway

While hair loss can occur with lorlatinib, it is not a common adverse effect and should not be a major concern when considering this medication for appropriate patients with ALK-positive NSCLC. The drug's efficacy profile, particularly in patients with brain metastases or those who have progressed on earlier-generation ALK inhibitors, generally outweighs this relatively uncommon side effect.