122P Primary results and biomarker analysis from PREDIX LumB: A prospective randomized phase II trial investigating sequence of neoadjuvant chemotherapy and palbociclib/endocrine therapy for luminal breast cancer

CDK4/6 inhibitors are approved for use at the adjuvant and metastatic settings of luminal breast cancer. Their place as preoperative treatment is under investigation. PREDIX Lum B (NCT02603679) is an academic prospective randomized phase II trial conducted in three sites in Sweden. Patients with hormone receptor positive (defined as ER ≥10%) and HER2-negative breast cancer measuring more than 20 mm and/or with lymph node metastasis were eligible for enrolment. Patients were randomized 1:1 to receive either paclitaxel weekly for 12 weeks followed by palbociclib and endocrine therapy for 12 weeks (Arm A), or the reverse sequence (Arm B). All patients received three cycles of adjuvant epirubicin and cyclophosphamide. Primary endpoint was rates of objective radiologic response at 12 weeks (ORR12). Secondary endpoints included pathologic complete response (pCR), event-free survival (EFS), safety, and health related quality of life (HRQoL) according to EORTC QLQ-C30 and QLQ-BR23. Between 2/2016 and 8/2021 181 patients were enrolled and 179 comprise the ITT population (39% premenopausal, 66% node positive). Median follow-up is 3.52 years. ORR12 was borderline higher in arm A (59% vs 45%, p=0.057). Baseline PET/CT SUVmax (OR=1.09, 95% CI 1.00 – 1.18, p=0.030), TILs (OR 1.19, 95% CI 1.00 – 1.42, p=0.05), and Ki67 (OR 1.03, 95% CI 1.00 – 1.06, p=0.031) correlated with ORR12. There was no difference between the two arms in pCR (3.3% vs 4.4%, p=0.700) or EFS (5-year rates 84.1% vs 84.9%, p=0.804). Of patients completing at least one treatment cycle, grade 3/4 adverse events were more common during palbociclib than paclitaxel (arm A: 40.2% vs 17.9%, arm B: 43.3% vs 13.6%), mostly due to neutropenia. However, HRQoL was better preserved during palbociclib than paclitaxel in both arms and returned to baseline levels at 18 months. Sequence of paclitaxel and palbociclib/endocrine therapy did not affect efficacy outcomes. Translational studies are ongoing to identify patients benefiting from treatment de-escalation.