Abstract PD8-03: Palbociclib and trastuzumab for HER2-positive metastatic breast cancer (SOLTI-1303 PATRICIA): Final results from cohort A and B, prospective, open-label, multicenter phase II study
Authors: Ciruelos Eva , Pascual Tomás , Oliveira Mafalda , Escrivá-de-Romaní Santiago , Pernas Sonia , Paré Laia , Adamo Barbara , Martínez Eduardo , Cortés Javier , Perelló Antonia , Galan Maria , Melé Mireia , Tolosa Pablo , González-Farré Blanca , Galván Patricia , Canes Jordi , Nuciforo Paolo , Gonzalez Xavier , Villagrasa Patricia , Prat Aleix 
Published: March 2022

Abstract
Background: CDK4/6 inhibition combined with anti-HER2 therapy is currently being explored in HER2-positive (HER2+) breast cancer (BC). Here, we report the final efficacy and genomic analysis of cohort A and B of the PATRICIA phase II trial evaluating palbociclib in combination with trastuzumab in advanced HER2+ BC. Methods: PATRICIA is a prospective, open-label, multicenter phase II trial. Patients had received 2-4 prior lines of anti-HER2-based regimens. Treatment consisted of palbociclib 200 mg daily for 2 weeks and 1 week off plus trastuzumab. The study was based on a Simon two-stage design comprising three cohorts: estrogen receptor (ER)-negative (cohort A), ER-positive (cohort B1), and ER-positive with letrozole (cohort B2). Patients with ER-positive tumors were randomized to cohorts B1 or B2. Primary endpoint was progression-free survival (PFS) rate at 6 months (PFS6). Secondary objectives included PFS, overall survival (OS) and the association of the research-based PAM50 intrinsic subtyping with PFS and OS. PAM50 was performed from FFPE samples using the nCounter platform. For each sample we calculated the PAM50 signature scores (Basal-like, HER2-E, Luminal A and B, Normal-like), CES, ROR-Subtype, ROR-proliferation and the proliferation signature score. Multivariable Cox regression analyses evaluating PAM50 subtypes, age, performance status, treatment line, type of biopsy, and ER status. Results: Seventy-one patients were recruited (n = 15 in cohort A and 28 in each cohort B). Median follow-up was 42.3 months (IQR 34.7-54.8). The PFS6 rate in cohorts A, B1, and B2 was 33.3% (5/15), 42.8% (12/28), and 46.4% (13/28), respectively. Median PFS was 4.2 months (95% CI 0.7-6.7) in cohort A, 6.0 months (95% CI 4.0-10.6) in cohort B1 and 5.1 months (95% CI 3.7-9.1) in cohort B2. Regarding PAM50, 59 (83.1%) tumors samples (42.4% metastasis) were profiled. 49.2% of the tumor samples were identified as HER2-E, followed by Luminal B (22.0%), Luminal A (16.9%), normal-like (10.2%), and Basal-like (1.7%). Luminal disease defined by PAM50 was independently associated with longer PFS compared with non-luminal disease (10.6 vs. 4.2 months median PFS; adjusted hazard ratio [HR] = 0.34; P = 0.007). Median OS was 21.8 months (95% CI 13.8-32.2) in cohort A, 28.0 months (95% CI 14.2-48.8) in cohort B1 and 34.3 months (95% CI 20.6-47.6) in cohort B2. Luminal disease defined by PAM50 was not independently associated with OS compared with non-luminal disease (34.3 vs. 26.1 months; adjusted HR = 0.753; P = 0.365). Among the 9 PAM50 signatures, expression of 3 signatures were found significantly associated with OS: CES (HR = 0.50; p=0.021), Luminal A score (HR=0.33; p=0.022) and ROR-S (HR=1.018; p=0.027). Conclusion: Our analysis shows that the promising PFS previously reported in trastuzumab pretreated ER-positive/HER2+ advanced breast cancer with a PAM50 Luminal A or B subtype were maintained after a median of &gt;3 years of follow-up. A longer OS was seen in patients with luminal tumors, but results were not statistically significant and could have been influenced by the low sample size. Cohort C of PATRICIA is currently randomizing patients with HR-positive/HER2+, PAM50 Luminal A or B tumors to palbociclib and endocrine therapy plus trastuzumab or treatment of physician’s choice (NCT02448420). Acknowledgements: This study is sponsored by SOLTI and financially supported by Pfizer
Citation Format: Eva Ciruelos, Tomás Pascual, Mafalda Oliveira, Santiago Escrivá-de-Romaní, Sonia Pernas, Laia Paré, Barbara Adamo, Eduardo Martínez, Javier Cortés, Antonia Perelló, Maria Galan, Mireia Melé, Pablo Tolosa, Blanca González-Farré, Patricia Galván, Jordi Canes, Paolo Nuciforo, Xavier Gonzalez, Patricia Villagrasa, Aleix Prat. Palbociclib and trastuzumab for HER2-positive metastatic breast cancer (SOLTI-1303 PATRICIA): Final results from cohort A and B, prospective, open-label, multicenter phase II study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD8-03.