ASCO Updates Clinical Guidelines for HER2+ Breast Cancer

Roxanne Nelson, BSN, RN

July 05, 2018

The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer.

In 2014, ASCO published evidence-based clinical practice guidelines (J Clin Oncol. 2014;32:2078-2099) on the optimal management of this population of patients with breast cancer. The goal of this update is to provide oncologists and other clinicians with current recommendations regarding treatment of these patients.

However, after an expert panel identified and reviewed 622 publications, they concluded that no results would change the 2014 guideline recommendations.

The updated guidelines are therefore almost unchanged and were published online June 25 in the Journal of Clinical Oncology.

Key Recommendations

The current recommendations for optimal medical therapy for patients with advanced HER2-positive breast cancer include the following:

  • HER2-targeted therapy–based combinations for first-line treatment should be recommended except for highly selected patients with estrogen receptor–positive or progesterone receptor–positive and HER2-positive disease. In those cases, endocrine therapy may be used alone (type: evidence based; evidence quality: high; strength of recommendation: strong).

  • If disease progresses during or after first-line HER2-targeted therapy, second-line HER2-targeted therapy–based treatment is recommended (type: evidence based; evidence quality: high; strength of recommendation: strong).

  • If disease progresses during or after second-line or greater HER2-targeted treatment, third-line or greater HER2-targeted therapy–based treatment is recommended (type: evidence based; evidence quality: intermediate; strength of recommendation: moderate).

  • Combination treatment with trastuzumab, pertuzumab, and a taxane is recommended for first-line treatment, unless taxanes are contraindicated (type: evidence based; evidence quality: high; strength of recommendation: strong).

  • If disease progresses during or after first-line HER2-targeted therapy, trastuzumab emtansine (T-DM1) is recommended as second-line treatment (type: evidence based; evidence quality: high; strength of recommendation: strong).

  • If disease progresses during or after second-line or greater HER2-targeted therapy but the patient has not received T-DM1, clinicians should offer T-DM1 (type: evidence based; evidence quality: high; strength of recommendation: strong).

  • For those already 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. HER2-targeted therapy should continue after chemotherapy is stopped, and no further change in the regimen is needed until progression or unacceptable toxicities (type: evidence based; evidence quality: intermediate; strength of recommendation: moderate).

  • If a patient finished trastuzumab-based adjuvant treatment 12 months or less before recurrence, the second-line HER2-targeted therapy–based treatment recommendations should be followed (type: evidence based; evidence quality: intermediate; strength of recommendation: moderate).

  • If trastuzumab-based adjuvant treatment is completed more than 12 months before recurrence, first-line HER2-targeted therapy–based treatment recommendations should be followed (type: evidence based; evidence quality: high; strength of recommendation: strong).

  • For hormone receptor–positive and HER2-positive disease, the following may be recommended:

    • 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).

ASCO has also added a qualifying statement: Although clinicians may discuss using endocrine therapy with or without HER2-targeted therapy, most patients will still receive chemotherapy plus HER2-targeted therapy.

Treatment for Brain Metastases

At the same time, ASCO has also updated its 2014 consensus-based guideline recommendations (J Clin Oncol. 2014;32:2100-2108) for the management of brain metastases in patients with HER-2 positive advanced breast cancer.

Once again, after a review of 622 articles, the expert panel found no additional evidence that would warrant a change to the previous recommendations.

The key recommendations include the following:

  • Options for patients with a favorable prognosis and a single brain metastasis include surgery with postoperative radiation, stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT with or without SRS), fractionated stereotactic radiotherapy (FSRT), and SRS (with or without WBRT); serial imaging every 2 to 4 months may be used to continue to monitor for local and distant brain failure.

  • Options for patients with a favorable prognosis for survival and limited (two to four) metastases include resection for large symptomatic lesion(s) plus postoperative radiotherapy, SRS for additional smaller lesions, WBRT (with or without  SRS), SRS (with or without  WBRT), and FSRT for metastases greater than 3 to 4 cm. For metastases less than 3 to 4 cm, options include resection with postoperative radiotherapy.

  • WBRT may be offered for patients with diffuse disease/extensive metastases and a more favorable prognosis or symptomatic leptomeningeal metastasis in the brain.

  • Options for patients with a poor prognosis include WBRT, best supportive care, and/or palliative care.

  • For patients with progressive intracranial metastases despite initial radiation therapy, options include SRS, surgery, WBRT, a trial of systemic therapy, or enrollment in a clinical trial.

  • For patients whose systemic disease is progressive at the time of brain metastasis diagnosis, HER2-targeted therapy is recommended.

  • Patients without a known history or symptoms of brain metastases should not undergo routine surveillance with brain MRI.

Several of the authors for both guidelines have disclosed relationships with industry.

J Clin Oncol. Published online June 25, 2018. Full text for advanced cancer guidelines; Full text for brain metastasis guidelines

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