Abstract OT2-02-03: NSABP FB-13: An assessment of the biological and clinical effects of palbociclib with ovarian suppression and letrozole in the neoadjuvant treatment of pts (pts) with premenopausal (preM) estrogen-receptor positive/HER2-negative primary breast cancer
Authors: Puhalla Shannon , Yothers Greg , Sing Amy P , Julian Thomas B , Wolmark Norman , Jacobs Samuel A 
Published: March 2020

Background: There have been few studies of neoadjuvant endocrine therapy in premenopausal (preM) women despite low pathologic complete response (pCR) rates using neoadjuvant chemotherapy in ER+/HER2− pts. Suppression of Ki67, particularly complete cell cycle arrest (CCCA) defined as Ki67 &lt;2.7% after 2 wks of neoadjuvant endocrine therapy has been demonstrated to correlate with recurrence-free survival. PALLET, a randomized, neoadjuvant endocrine trial evaluated letrozole (AI) v palbociclib (pal) in combination with AI for 14 wks in post-menopausal women. This study demonstrated a modest improvement in clinical response (54.3% with the combination v 49.5% with AI alone) but showed a significant difference in achievement of CCCA (Ki67&lt;2.7%) with the combination of pal and AI v AI alone (90% v 59%). We seek to evaluate this combination, given over a longer duration in the neoadjuvant setting, in preM women with early-stage breast cancer. Trial design: FB-13 is a phase II, open-label study to examine the biological and clinical effect of neoadjuvant endocrine therapy with AI, pal, and ovarian suppression in preM pts with ER+, HER2-negative early invasive breast cancer. 76 pts will be stratified into one of two approximately equal sized cohorts based on Oncotype DX Breast Recurrence Score (RS) (cohort 1: pts with RS &lt;11 or cohort 2: pts with RS 11 to &lt;26). A baseline tumor biopsy prior to start of therapy (tx) for RS and Ki67 will both be centrally determined. Pts in both cohorts will receive letrozole 2.5 mg by mouth daily, pal 125 mg by mouth daily for 21 days of a 28-day cycle, and goserelin 3.6 mg SQ injection every 28 days. At wk 6, pts will have core-cut biopsies for real-time evaluation of Ki67. Pts from both cohorts who have Ki67 &lt;10% will continue tx for a total of 6 cycles. Pts with a persistent Ki67 ≥10% will permanently discontinue tx and begin neoadjuvant chemotherapy or proceed to surgery at physician discretion. Eligibility: FB-13 is enrolling preM women newly diagnosed with ER+/HER2− early breast cancer who are candidates for neoadjuvant endocrine therapy. Pts must be preM based on standard definitions. Primary tumor size must be &gt;2 cm. RS must be &lt;26. Mandatory pre-treatment and post-surgical samples will be collected and analyzed for RS and Ki67, as well as additional biomarkers to correlate with response. Blood will be collected at baseline, 4 wks, and at 24 wks for estradiol levels to demonstrate ovarian suppression. A 4-wk estradiol level in the postmenopausal range will be required to receive further treatment. Specific aims: The primary aim is to determine complete cell cycle arrest as indicated by a Ki67 &lt;2.7% at 6 wks. Secondary aims are to determine overall response rate (ORR) by clinical exam and ultrasound, the pCR, to generate a Preoperative Endocrine Prognostic Index (PEPI score), to compare the change in Ki67 at baseline, after 6 wks and 24 wks, and to determine the rate of breast-conservation therapy. Statistical methods: We anticipate that the addition of palbociclib to ovarian suppression and AI will result in a measurable drop in Ki67 and a high ORR. The null hypothesis is ORR &lt;40% and alternative hypothesis is ORR &gt;60%. We anticipate that &gt;60% of pts in each cohort will have 6 wk Ki67 &lt;2.7% and clinical response &gt;35%. Present accrual and target accrual: Currently 12 of a planned 76 pts have been enrolled. NSABP Operations contact information: Diana Gosik, Diana.Gosik@nsabp.org NCT03628066 SUPPORT: Genomic Health Inc, Pfizer, NSABP Foundation

Citation Format: Shannon Puhalla, Greg Yothers, Amy P Sing, Thomas B Julian, Norman Wolmark, Samuel A Jacobs. NSABP FB-13: An assessment of the biological and clinical effects of palbociclib with ovarian suppression and letrozole in the neoadjuvant treatment of pts (pts) with premenopausal (preM) estrogen-receptor positive/HER2-negative primary breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-02-03.