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Traditional systemic chemotherapy superior to targeted treatment for HER-2-positive breast cancer

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January 12, 2018

Sara A. Hurvitz

Patients with HER-2-positive breast cancer appeared more likely to achieve pathologic complete response when treated with traditional neoadjuvant systemic chemotherapy plus HER-2-targeted blockade than HER-2-targeted chemotherapy plus HER-2-targeted blockade, according to results of the open-label, randomized phase 3 KRISTINE trial.

However, more grade 3 or grade 4 adverse events occurred among patients assigned traditional neoadjuvant systemic chemotherapy.

Use of trastuzumab (Herceptin, Genentech)-based regimens in the neoadjuvant setting has resulted in pathologic complete response rates of 30% to 45% among patients with HER-2-positive breast cancer, according to Sara A. Hurvitz, MD, director of the breast oncology program at UCLA Jonsson Comprehensive Cancer Center, and colleagues.

“Findings from previous studies have shown that dual-agent HER-2 blockade increases the number of patients achieving a pathological complete response compared with single-agent HER-2-directed treatment,” Hurvitz and colleagues wrote. “[Among] patients with HER-2-positive early breast cancer ... incorporation of highly effective anti-HER-2 therapies has led to 3-year survival rates in excess of 90%.”

Researchers conducted the KRISTINE trial to assess a neoadjuvant regimen for HER-2-positive breast cancer that replaced traditional systemic chemotherapy with targeted treatment.

The analysis included 444 patients aged 18 years or older with HER-2-positive stage II to stage III operable breast cancer. All patients had ECOG performance status of 0 or 1, and a baseline left ventricular ejection fraction of at least 55%.

Researchers randomly assigned 221 patients to traditional neoadjuvant systemic chemotherapy with docetaxel (75 mg/m2) and carboplatin (area under the concentration-time curve, 6 mg/mL per minute), plus HER-2 targeted blockade with trastuzumab (8-mg/kg loading dose, followed by 6-mg/kg maintenance doses) and pertuzumab (Perjeta, Genentech), administered in an 840-mg loading dose and 420-mg maintenance doses.

The other 223 patients received six cycles of the experimental regimen, which consisted of 3.6 mg/kg ado-trastuzumab emtansine (Kadcyla, Genentech) plus pertuzumab (840-mg loading dose, followed by 420-mg maintenance doses).

Pathologic complete response, measured by local evaluation of tumor samples taken at breast cancer surgery — performed 14 days to 6 weeks after completion of neoadjuvant therapy — served as the primary endpoint. Researchers also assessed safety among all patients who received at least one dose of study medication.

A higher percentage of patients assigned traditional systemic chemotherapy regimen achieved pathologic complete response (55.7% vs. 44.4%; absolute difference, – 11.3 percentage points; 95% CI, –20.5 to –2). However, grade 3 to grade 4 adverse events (64% vs. 13%) and serious adverse events (29% vs. 5%) occurred more frequently in the group assigned traditional systemic chemotherapy.

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Patients assigned traditional systemic chemotherapy appeared more likely to experience grade 3 to grade 4 neutropenia (25% vs. <1%), diarrhea (15% vs. <1%), febrile neutropenia (15% vs. 0%), platelet count decrease (5% vs. 1%), fatigue (3% vs. 1%), alanine aminotransferase increase (2% vs. 1%) and hypokalemia (2% vs. 1%).

Researchers reported no deaths in either group during neoadjuvant treatment.

“In the neoadjuvant setting, where the ultimate aim of treatment is to prevent disease recurrence, the use of HER-2 blockade plus traditional chemotherapy remains the standard therapeutic approach to optimizing the number of patients achieving a pathological complete response,” Hurvitz and colleagues wrote. “Future efforts should improve the efficacy of chemotherapy without imparting more toxicity.” – by Savannah Demko

Disclosures: Hurvitz reports honoraria from F. Hoffmann-La Roche and Genentech, as well as travel support from Bayer, Boehringer Ingelheim, Eli Lilly, F. Hoffmann-La Roche, Novartis and Pfizer. Please see the study for all other authors’ relevant financial disclosures.