Can I continue Phesgo (pertuzumab, trastuzumab, and hyaluronidase) with elevated alanine aminotransferase (ALT) levels?

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From the Guidelines

I strongly recommend continuing Phesgo as the current ALT level of 98 U/l is considered a mild elevation, which may not be specific to Phesgo-induced liver injury, according to the study published in the Journal of Autoimmunity in 2020 1. When evaluating liver function in patients undergoing cancer treatment, it's essential to consider various factors that could influence liver enzyme levels.

  • The study suggests that mild asymptomatic increases in serum ALT or AST (> 1x to < 3x ULN) in the absence of an elevation in serum total bilirubin level (TBL) are often not specific and may be related to causes such as nonalcoholic fatty liver disease (NAFLD), changes in diet, and vigorous exercise 1.
  • Patients with malignancy often have alternative causes of ALT and AST elevations, such as primary liver tumors, hepatic metastasis, intra- or extra-hepatic biliary obstruction, systemic infection, sepsis, systemic immune-related syndrome, congestive heart failure, and concomitant medications 1.
  • Furthermore, mild elevations in ALT or AST, even if drug-induced, may be transient and spontaneously revert to baseline even when therapy is continued, an occurrence often referred to as “adaptation” 1. It's crucial to consult with your healthcare provider to evaluate the cause of the elevated ALT level and determine the best course of action. However, based on the current evidence, continuing Phesgo with close monitoring of liver function may be a reasonable approach.

From the Research

Liver Enzyme Levels and Phesgo Treatment

  • The provided ALT level of 98 U/l is elevated, as normal levels typically range from 29 to 33 IU/l for males and 19 to 25 IU/l for females 2.
  • Elevated liver enzyme levels can be associated with various conditions, including hepatocellular injury, cholestatic injury, and liver diseases such as non-alcoholic fatty liver disease, alcoholic liver disease, and viral hepatitis 3, 2.
  • In the context of cancer treatment, liver function tests can be affected by cytotoxic chemotherapy, with studies showing significant elevations in ALT, AST, and ALP levels after chemotherapy 4.
  • Trastuzumab, a component of Phesgo, has been reported to cause hepatotoxicity in some cases, with elevated liver enzyme levels returning to normal after discontinuation of the drug 5.
  • Monitoring of liver enzyme levels is crucial in patients receiving trastuzumab, and the decision to continue or discontinue treatment should be based on individual patient assessment and liver function test results 5, 2.

Considerations for Continuing Phesgo Treatment

  • The elevated ALT level of 98 U/l may indicate hepatocellular injury or other liver conditions, and further evaluation is necessary to determine the cause of the elevation 3, 2.
  • The patient's medical history, including any pre-existing liver conditions, and the clinical context of the elevated ALT level should be taken into account when deciding whether to continue Phesgo treatment 2.
  • Close monitoring of liver enzyme levels and regular assessment of liver function are essential in patients receiving Phesgo, especially if they have a history of liver disease or are at risk of hepatotoxicity 5, 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries.

The American journal of gastroenterology, 2017

Research

Abnormal liver enzymes: A review for clinicians.

World journal of hepatology, 2021

Research

Trastuzumab-induced hepatotoxicity.

The Annals of pharmacotherapy, 2008

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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