ASCO Releases Clinical Practice Guideline on Systemic Therapy for Patients With Advanced HER2-Positive Breast Cancer
Approximately 15% of patients with breast cancer have tumors that overexpress the HER2 protein, and these patients can benefit from HER2-targeted therapies. The American Society of Clinical Oncology recently released a clinical practice guideline on systemic therapy for patients with advanced HER2-positive breast cancer, published in the Journal of Clinical Oncology. The rationale for the guideline is that several new agents have become available for treatment of metastatic HER2-positive breast cancer since the approval of trastuzumab (Herceptin). Up to half of patients with HER2-positive metastatic breast cancer develop brain metastases over time. Recommendations for the management of brain metastases in patients with HER2-positive breast cancer are detailed in a recently released companion guideline.
The guideline recommendations were developed by a multidisciplinary group of experts based on a systematic review of phase III randomized controlled trials and clinical experience. Literature searches identified a total of 16 eligible randomized controlled trials reported between 2009 and 2012, consisting of nine first-line, three second-line, and four post–second-line trials. Three first-line hormonal therapy plus HER2-targeted therapy trials addressed the role of hormonal/endocrine therapy, and two trials addressed the issue of how prior adjuvant HER2-targeted therapy might influence subsequent treatment choices. Outcomes of interest included overall survival, progression-free survival, and adverse events.
The ASCO expert panel was co-chaired by Sharon H. Giordano, MD, of The University of Texas MD Anderson Cancer Center, and Eric P. Winer, MD, of Dana-Farber Cancer Institute.
Primary Clinical Question
The primary clinical question addressed by the guideline is: “What is the optimal medical therapy for advanced HER2-positive breast cancer, specifically HER2-targeted therapy, either alone or in combination with chemotherapy and/or endocrine therapy?” The guideline recommendations are summarized below, along with notation of type of recommendation, evidence quality, and strength of recommendation.
Recommendations
General Recommendations
- Clinicians should recommend HER2-targeted therapy–based combinations for first-line treatment, except in highly selected patients with estrogen receptor–positive or progesterone receptor–positive and HER2-positive disease; in such patients, endocrine therapy alone may be used. (Type = evidence based; evidence quality = high; strength of recommendation = strong.)
- For patients with disease progressing during or after first-line HER2-targeted therapy, clinicians should recommend second-line HER2-targeted therapy–based treatment. (Type = evidence based; evidence quality = high; strength of recommendation = strong.)
- For patients with disease progressing during or after second-line or greater HER2-targeted treatment, clinicians should recommend third-line or greater HER2-targeted therapy–based treatment. (Type = evidence based; evidence quality = intermediate; strength of recommendation = moderate.)
Specific Regimens
- Clinicians should recommend the combination of trastuzumab, pertuzumab (Perjeta), and a taxane for first-line treatment, unless the patient has a contraindication to taxanes. (Type = evidence based; evidence quality = high; strength of recommendation = strong.)
- For patients with disease progressing during or after first-line HER2-targeted therapy, clinicians should recommend ado-trastuzumab emtansine (Kadcyla) as second-line treatment. (Type = evidence based; evidence quality = high; strength of recommendation = strong.)
- For patients with disease progressing during or after second-line or greater HER2-targeted therapy who have not received ado-trastuzumab emtansine, clinicians should offer ado-trastuzumab emtansine. (Type = evidence based; evidence quality = high; strength of recommendation = strong.)
- For patients with disease progressing during or after second-line or greater HER2-targeted treatment who have not received pertuzumab, clinicians may offer pertuzumab. (Type = informal consensus; evidence quality = insufficient; strength of recommendation = weak.)
- For patients with disease progressing during or after second-line or greater HER2-targeted treatment who have already received pertuzumab and ado-trastuzumab emtansine, clinicians should recommend third-line or greater HER2-targeted therapy–based treatment. Options include lapatinib plus capecitabine, as well as other combinations of chemotherapy, and trastuzumab, lapatinib (Tykerb), and trastuzumab, or hormonal therapy (in patients with estrogen receptor–positive and/or progesterone receptror–positive disease). There is insufficient evidence to recommend one regimen over another. (Type = informal consensus, evidence quality = insufficient, strength of recommendation = weak.)
Chemotherapy Duration
In patients receiving HER2-targeted therapy and chemotherapy combinations, 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 HER2-targeted therapy; no further change in the regimen is needed until the time of progression or unacceptable toxicities. (Type = evidence based; evidence quality = intermediate; strength of recommendation = moderate.)
Patients Who Received Adjuvant Trastuzumab
- For patients finishing trastuzumab-based adjuvant treatment ≤ 12 months before recurrence, clinicians should follow the second-line HER2-targeted therapy–based treatment recommendations. (Type = evidence based; evidence quality = intermediate; strength of recommendation = moderate.
- For patients finishing trastuzumab-based adjuvant treatment > 12 months before recurrence, clinicians should follow the first-line HER2-targeted therapy–based treatment recommendations. (Type = evidence based; evidence quality = high; strength of recommendation = strong.)
Endocrine Therapy
- For patients with hormone receptor–positive and HER2-positive disease, clinicians may recommend:
- HER2-targeted therapy plus chemotherapy. (Type = evidence based; evidence quality = high; strength of recommendation = strong.)
- Endocrine therapy plus trastuzumab or lapatinib (in selected cases). (Type = evidence based; evidence quality = high; strength of recommendation = moderate.)
- Endocrine therapy alone (in selected cases). (Type = evidence based; evidence quality = intermediate; strength of recommendation = weak.)
- For patients who have started with a HER2-positive targeted therapy and chemotherapy combination, clinicians may add endocrine therapy to the HER2-targeted therapy when chemotherapy ends and/or when the cancer progresses. (Type = informal consensus; evidence quality = insufficient; strength of recommendation = weak.)
- In special circumstances, such as low disease burden, presence of comorbidities (contradictions to HER2-targeted therapy such as congestive heart failure), and/or presence of a long disease-free interval, clinicians may offer first-line endocrine therapy alone. (Type = informal consensus; evidence quality = intermediate; strength of recommendation = weak.)
- 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.
For full disclosures of the study authors, visit jco.ascopubs.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®.
