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ASCO Clinical Practice Guideline Update: Systemic Therapy for Patients With Advanced HER2-Positive Breast Cancer

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As reported in the Journal of Clinical Oncology by Sharon H. Giordano, MD, of The University of Texas MD Anderson Cancer Center, and colleagues, ASCO has released a clinical practice guideline update on systemic therapy for patients with advanced HER2-positive breast cancer. The guideline update was informed by an expert panel targeted systematic literature review that identified 622 relevant articles. The expert panel was co-chaired by Dr. Giordano and Nancy E. Davidson, MD, of the Fred Hutchinson Cancer Research Center and University of Washington.

Among the 622 publications reviewed, no additional evidence was identified that warranted substantive changes to the 2014 recommendations. Key current recommendations are produced or summarized below.

Key Recommendations

  • Clinicians should recommend HER2-targeted therapy–based combinations for first-line treatment, except for highly selected patients with estrogen receptor (ER)-positive or progesterone receptor (PR)-positive and HER2-positive disease, for whom clinicians may use endocrine therapy alone.
  • If a patient’s HER2-positive advanced breast cancer has progressed during or after first-line HER2-targeted therapy, clinicians should recommend second-line HER2-targeted therapy–based treatment.
  • If a patient’s HER2-positive advanced breast cancer has progressed during or after second-line or greater HER2-targeted treatment, clinicians should recommend third-line or greater HER2-targeted therapy–based treatment.
  • Clinicians should recommend the combination of trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane for first-line treatment, unless the patient has a contraindication to taxanes.
  • If a patient’s HER2-positive advanced breast cancer has progressed during or after first-line HER2-targeted therapy, clinicians should recommend ado-trastuzumab emtansine (aka T-DM1; Kadcyla) as second-line treatment.
  • If a patient’s HER2-positive advanced breast cancer has progressed during or after second-line or greater HER2-targeted therapy, but she has not received T-DM1, clinicians should offer T-DM1.
  • If a patient’s HER2-positive advanced breast cancer has progressed during or after second-line or greater HER2-targeted treatment, but she has not received pertuzumab, clinicians may offer pertuzumab.
  • If a patient’s HER2-positive advanced breast cancer has progressed during or after second-line or greater HER2-targeted treatment, and she has already received pertuzumab and T-DM1, clinicians should recommend third-line or greater HER2-targeted therapy–based treatment. Options include lapatinib (Tykerb) plus capecitabine, as well as other combinations of chemotherapy, and trastuzumab, lapatinib, and trastuzumab, or hormonal therapy (in patients with ER-positive and/or PR-positive disease). There is insufficient evidence to recommend one regimen over another.
  • If a patient is receiving HER2-targeted therapy and chemotherapy combinations, the chemotherapy should continue for approximately 4 to 6 months (or longer) and/or to the time of maximal response, depending on toxicity and in the absence of progression. When chemotherapy is stopped, clinicians should continue the HER2-targeted therapy; no further change in the regimen is needed until the time of progression or unacceptable toxicities.
  • If a patient finished trastuzumab-based adjuvant treatment less than or equal to 12 months before recurrence, clinicians should follow the second-line HER2-targeted therapy–based treatment recommendations.
  • If a patient finished trastuzumab-based adjuvant treatment more than 12 months before recurrence, clinicians should follow the first-line HER2-targeted therapy–based treatment recommendations.
  • If a patient’s cancer is hormone receptor–positive and HER2-positive, clinicians may recommend either:
    •  HER2-targeted therapy plus chemotherapy
    •  Endocrine therapy plus trastuzumab or lapatinib (in selected cases)
    •  Endocrine therapy alone
  • If a patient has started with a combination of HER2-positive targeted therapy and chemotherapy, clinicians may add endocrine therapy to the HER2-targeted therapy when chemotherapy ends and/or when the cancer progresses.
  • In special circumstances, such as low disease burden, presence of comorbidities (eg, contraindications to HER2-targeted therapy such as congestive heart failure), and/or the presence of a long disease-free interval, clinicians may offer first-line endocrine therapy alone.

Qualifying statement: Although clinicians may discuss using endocrine therapy with or without HER2-targeted therapy, the majority of patients will still receive chemotherapy plus HER2-targeted therapy.

Additional information is available at www.asco.org/breast-cancer-guidelines.

The corresponding author for the Journal of Clinical Oncology article is ASCO; e-mail: guidelines@asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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