Trastuzumab emtansine provides effective, less toxic neoadjuvant therapy for HER2-positive breast cancer

CHICAGO — Trastuzumab emtansine appeared as effective as, but less toxic than, docetaxel, trastuzumab and pertuzumab as neoadjuvant therapy for HER2-positive breast cancer, according to results of a randomized phase 2 study presented at ASCO Annual Meeting.

Although neoadjuvant therapy induces high rates of pathologic complete response and is standard of care for HER2-positive breast cancer, the optimal therapy is not established.

The combination of trastuzumab (Herceptin, Genentech), pertuzumab (Perjeta, Genentech) and chemotherapy is associated with a pathologic response rate ranging from 45% to 80%, depending on breast cancer subtype.

Previous data showed trastuzumab emtansine (Kadcyla, Genentech) conferred a median survival gain of 6.9 months among patients who previously failed two or more anti-HER2 therapies.

Jonas C. S. Bergh, FRCP, MD, PhD, professor in oncology at Karolinska Institutet and University Hospital in Sweden, and colleagues sought to evaluate the use of trastuzumab emtansine as neoadjuvant therapy, as there has been potential concern regarding its effect in a population with variable HER2 protein expression.

The analysis included 199 patients with HER2-positive breast cancer larger than 20 mm or verified lymph node metastases.

Researchers assigned patients to six courses of docetaxel, trastuzumab and pertuzumab (group A; n = 100; median age, 51 years; range, 26-73) or trastuzumab emtansine (group B; n = 99; median age, 53 years; range, 28-74). Patients could switch treatment arms if they experienced severe toxicity or did not respond to treatment.

Sixty-six percent of patients in group A were ER and/or PR positive, as were 60% of patients in group B.

All patients received postoperative epirubicin plus cyclophosphamide every 3 weeks, plus trastuzumab for 11 courses. Patients who were ER or PR positive also received endocrine therapy for 5 to 10 years.

Pathologic complete response served as the study’s primary endpoint.

Results showed 47% of group A and 45% of group B achieved pathologic complete response. Among those with hormone receptor-negative disease, rates of pathologic complete response were 67% in group A and 59% in group B. For the hormone receptor-positive groups, pathologic complete response rates were 36% in both groups.

Eighteen patients switched from group A to group B for treatment, 14 of whom switched due to toxicity. Nine patients switched from group B to group A, two of whom switched due to toxicity. One patient in each group achieved pathologic complete response after switching to the other group.

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Adverse events that occurred more frequently in group A included febrile neutropenia (grade 3-4, 26%), infection (grade 1-2, 15%; grade 3-4, 11%), mucositis (grade 1-2, 53%), diarrhea (grade 1-2, 59%; grade 3-4, 14%), colitis (grade 3-4, 6%), sensory neuropathy (grade 1-2, 30%), edema (grade 1-2, 11%) and exanthema (grade 1-2, 44%). Liver toxicity (grade 1-2, 14%; grade 3-4, 6%) was the only toxicity to occur more frequently in group B.

In a separately reported analysis, researchers also observed better quality of life among patients in group B, Bergh said.

Researchers conducted an exploratory analysis that showed relative decrease in ¹⁸F-FDG uptake after two treatment courses may be indicative of pathologic complete response, suggesting PET/CT can be used to predict outcomes. – by Alexandra Todak

Reference:

Bergh JCS, et al. Abstract 501. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosure: Bergh reports research funding to his institution from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche and Sanofi, and another financial relationship with UpToDate. Please see the abstract for all other authors’ relevant financial disclosures.