Chemotherapy-free regimen in Ki67 responders ‘warrants further investigation’

De-escalated treatment with trastuzumab, pertuzumab and letrozole an effective, chemotherapy-free regimen for patients with hormone receptor-positive, HER-2-, operable breast cancer, according to findings from the PerELISA neoadjuvant study presented at the ASCO Annual Meeting.

“Neoadjuvant trials with chemotherapy plus anti-HER-2 agents consistently showed a lower rate of pathologic complete response in HER-2-positive, hormone receptor-positive vs. HER-2-positive, hormone receptor-negative tumors,” the researchers wrote. “Here, we report the final results of the PerELISA study, aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HER-2-positive, hormone-receptor positive patients selected on the basis of Ki67 response after a short course [of] letrozole.”

Valentina Guarneri, MD, PhD, associate professor of oncology at the University of Padua and attending physician in the Division of Medical Oncology 2 at the Istituto Oncologico Veneto in Italy, and colleagues conducted this phase 2, multicenter, non-profit study in postmenopausal women with operable HER-2-positive, HR-positive breast cancer. Researchers based patient selection on Ki67 response after a short course of treatment with letrozole.

Following window therapy with letrozole for 2 weeks, the researchers re-biopsied patients to assess Ki67 status. Individuals with a relative reduction in Ki67 (20% from baseline) were deemed Ki67 responders. These patients continued treatment with letrozole and began receiving trastuzumab and pertuzumab every 21 days for 5 cycles. Individuals who did not achieve a Ki67 response stopped treatment with letrozole and initiated weekly paclitaxel, in combination with trastuzumab and pertuzumab, for 13 weeks.

The primary objective of the study was breast and axillary pathologic complete response. A minimum of pathologic complete responses among 43 patients classified as Ki67 responders were necessary to achieve the study premise. Correlative analyses comprised PAM50, tumor-infiltrating lymphocytes and PIK3CA.

The trial included 64 patients with a median age of 63 years (range, 49-83 years) from centers. Most patients (67%) had stage IIA disease; 23% had stage IIB disease and 9% had stage IIIA disease.

Median ER, progesterone receptor and Ki67 expression was 90% (range, 10% to 100%), 14% (0% to 100%) and 30% (7% to 90%), respectively. The median level of tumor-infiltrating lymphocytes was 10% (Q1, 2%; Q3, 15%). PIK3CA mutations were observed in 25% of cases.

Following 2 weeks of window therapy with letrozole, 44 patients (69%) reached a Ki67 response. Those responders began treatment with letrozole, trastuzumab and pertuzumab and then had surgery, which included breast-conserving procedures in 66% of patients and mastectomy in 34% of patients. Pathologic complete responses, which were “significantly” higher in patients with HER-2-enriched disease compared with other subtypes (45.5% vs. 13.8%; P = .042), were seen in cases (20.5%).

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The intrinsic subtype was “significantly associated” with a Ki67 response (P < .001). , a Ki67 response was more common in patients with the luminal subtype (92.6%) compared with the non-luminal subtype (44%).

“The study met its primary aim. A chemotherapy-free regimen for patients with Ki67 response after short-term letrozole warrants further investigation,” the researchers wrote. “Among Ki67 responders, the HER-2-enriched subtype can identify patients most likely to benefit from de-escalated therapy.” – by Julia Ernst, MS

Reference:

Guarneri VG, et al. Abstract 507. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Disclosures: Guarneri reports serving in a consultant or advisory role for Eli Lilly and receiving research funding through her institution from Roche and travel, accommodations and expenses from AstraZeneca and Celgene. Please see the study for all other authors’ relevant financial disclosures.