Results from a multicenter phase II study of patients with locally advanced HER2-positive breast cancer who receive targeted therapy with trastuzumab (Herceptin) and lapatinib (Tykerb) “support the hypothesis that selected patients with HER2-positive tumors may not need chemotherapy,” investigators reported in the Journal of Clinical Oncology.
Women with stage II or III HER2-positive breast cancers received trastuzumab once per week (4 mg/kg loading dose, then 2 mg/kg) and lapatinib at 1,000 mg once daily for 12 weeks. Women with estrogen receptor (ER)-positive tumors also received letrozole, plus a luteinizing hormone–releasing hormone agonist if premenopausal. The median age of the patients was 49 years, and the range was 31 to 74 years. “The study enrolled patients with large tumors, with a median tumor size of 6 cm (range, 1.5 to 30 cm), and 62% of patients had tumors that were > 5 cm,” the researchers noted.
‘Clinically Meaningful’ Pathologic Complete Response Rate
The overall pathologic complete response, defined as disappearance of invasive cancer in the breast, among the 64 patients evaluable for response was 27%, including 21% in the ER-positive group and 36% in the ER-negative group. “Here, we show in a neoadjuvant clinical trial in patients with locally advanced HER2-positive tumors that a potent cocktail of drugs that more completely blocks the HER network causes [pathologic complete response] in the breast in a substantial percentage of patients. Achieving this rate of [pathologic complete response] with targeted therapy only and without using chemotherapy is noteworthy and clinically meaningful,” the authors wrote.
While “a subset of patients derived substantial clinical benefit from the 12-week treatment despite large initial tumor size,” the researchers noted, “some of them, especially those with ER-positive tumors, still had minimal residual disease at the time of surgery. The rate of low-volume residual disease was 22%, including 33% in the ER-positive group and 4% in the ER-negative group. Overall, 89% of patients proceeded to surgery after completing the study treatment, although some received additional neoadjuvant therapy before surgery.
“The study treatment was generally well tolerated,” the researchers reported. “Treatment was discontinued because of toxicity in only 6% of patients. The most common toxicities were diarrhea (grades 1 to 2, 63%; grades 3 to 4, 3%) followed by rash (grades 1 to 2, 55%; grades 3 to 4, 1%), fatigue (32%), nausea (31%), and elevated liver function tests (grades 1 to 2, 18%; grade 3, 5%; grade 4, 2%). Only one grade 4 toxicity was observed in the study (elevated liver function tests), which completely normalized after 8 weeks.”
The investigators noted that the study needs to be validated in a large setting but concluded that the “results raise the prospect of sparing a subset of patients in the future the toxicity and cost of chemotherapy, a worthy and meaningful goal.”
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