Abstract 122P
Background
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.
Methods
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.
Results
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.
Conclusions
Sequence of paclitaxel and palbociclib/endocrine therapy did not affect efficacy outcomes. Translational studies are ongoing to identify patients benefiting from treatment de-escalation.
Clinical trial identification
NCT02603679.
Legal entity responsible for the study
Karolinska University Hospital.
Funding
Swedish Cancer Society (Cancerfonden), Swedish Breast Cancer Association (Bröstcancerförbundet), Swedish Research Council (Vetenskapsrådet), The Research Funds at Radiumhemmet, Pfizer.
Disclosure
A. Matikas: Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker, International co-PI of academic trial ARIADNE (EU CT: 2022-501504-95-00): AstraZeneca, Novartis, Veracyte; Financial Interests, Institutional, Invited Speaker, Registry study: Merck; Non-Financial Interests, Advisory Role: Veracyte, Roche. J. Hartman: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Lilly, MSD; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Novartis; Financial Interests, Personal, Ownership Interest: Stratipath. J. Bergh: Other, Fees (honoraria) to Coronis and Asklepios Cancer Research AB as an invited speaker/chair from AstraZeneca and Roche, respectively: Coronis and Asklepios Cancer Research AB.; Other, Institutional honoraria as chapter co-author for UpToDate to Asklepios Medicin HB. Co-author on a chapter on ”Prognostic and Predictive factors in early, non-metastatic breast cancer”: Asklepios Medicin; Other, Institutional research grants received more than ten years ago to Karolinska Institutet and/or University Hospital for molecular marker studies/ clinical studies (we are still working with the material). No personal payments for these activities: Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche and Sanofi-Aventis; Other, Stocks in Stratipath AB. The company is involved in AI based diagnostics for breast cancer: Stratipath AB. T. Hatschek: Financial Interests, Personal, Advisory Board, Meeting of a group of specialists for discussion on translational research twice yearly: Pfizer; Financial Interests, Institutional, Invited Speaker, Grants related to the academic PREDIX LumB trial: Pfizer. T. Foukakis: Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Expert Testimony: Affibody; Financial Interests, Personal, Royalties, Authorship of two chapters in UpToDate: Wolters Kluwer; Financial Interests, Institutional, Invited Speaker, Clinical trial support (research grant and study drug): Pfizer, AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical trial support (research grant and study drug): Novartis. All other authors have declared no conflicts of interest.