What is the optimal medical therapy for advanced HER2-positive breast cancer ?


The aim of American Society of Clinical Oncology ( ASCO ) Clinical Practice Guideline is to provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 ( HER2 ) –positive advanced breast cancer.

The ASCO convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic literature review from January 2009 to October 2012. Outcomes of interest included overall survival, progression-free survival, and adverse events.

A total of 16 trials met the systematic review criteria. The CLEOPATRA trial found survival and progression-free survival benefits for Docetaxel, Trastuzumab, and Pertuzumab in first-line treatment, and the EMILIA trial found survival and progression-free survival benefits for Trastuzumab emtansine ( T-DM1 ) in second-line treatment.
T-DM1 also showed a third-line progression-free survival benefit.
One trial reported on duration of HER2-targeted therapy, and three others reported on endocrine therapy for patients with HER-positive advanced breast cancer.

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 ( PgR ) –positive and HER2-positive disease, for whom clinicians may use endocrine therapy alone. Type: evidence based. Evidence quality: high. Strength of recommendation: strong.

● 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. Type: evidence based. Evidence quality: high. Strength of recommendation: strong.

● 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. Type: evidence based. Evidence quality: intermediate. Strength of recommendation: moderate.

● Clinicians should recommend the combination of Trastuzumab, Pertuzumab, 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.

● If a patient’s HER2-positive advanced breast cancer has progressed during or after first-line HER2-targeted therapy, clinicians should recommend Trastuzumab emtansine ( T-DM1 ) as second-line treatment. Type: evidence based. Evidence quality: high. Strength of recommendation: strong.

● 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. Type: evidence based. Evidence quality: high. Strength of recommendation: strong.

● 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. Type: informal consensus. Evidence quality: insufficient. Strength of recommendation: weak.

● 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 plus Capecitabine, as well as other combinations of chemotherapy, and Trastuzumab, Lapatinib and Trastuzumab, or hormonal therapy ( in patients with ER-positive and/or PgR-positive disease ). There is insufficient evidence to recommend one regimen over another. Type: informal consensus. Evidence quality: insufficient. Strength of recommendation: weak.

● 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. Type: evidence based. Evidence quality: intermediate. Strength of recommendation: moderate.

● If a patient finished Trastuzumab-based adjuvant treatment less than or equal to 12 months before recurrence, clinicians should follow the secondline HER2-targeted therapy-based treatment recommendations. Type: evidence based. Evidence quality: intermediate. Strength of recommendation: moderate.

● If a patient finished trastuzumab-based adjuvant treatment greater than 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.

● If a patient’s cancer is hormone receptor positive and HER2 positive, clinicians may recommend either:

● 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.

● If a patient has started with an 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.

Source: Journal of Clinical Oncology, 2014

XagenaMedicine_2014



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