Abstract PD3-03: SOLTI-1303 PATRICIA phase II trial (STAGE 1) -- Palbociclib and trastuzumab in postmenopausal patients with HER2-positive metastatic breast cancer
Authors: Ciruelos E , Villagrasa P , Paré L , Oliveira M , Pernas S , Cortés J , Soberino J , Adamo B , Vazquez S , Martínez N , Perelló A , Bermejo B , Martínez E , Garau I , Melé M , Morales S , Galván P , Pascual T , Canes J , Nuciforo P , Gonzalez X , Prat A 
Published: May 2019

Abstract
Background: CDK4/6 inhibition combined with anti-HER2 therapy is currently being explored in HER2-positive (HER2+) BC. Here, we report the efficacy, safety and genomic analysis of STAGE 1 of the PATRICIA phase II trial evaluating palbociclib in combination with trastuzumab (TTZ) in advanced HER2+ BC.
Methods: PATRICIA is an exploratory, prospective, open-label, multicenter phase II trial. Patients (pts) had received 2-4 prior lines of anti-HER2-based regimens. Treatment consisted of TTZ 6 mg/kg every 3w and palbociclib 200 mg daily for 2w and 1w off. The study was based on a Simon 2-stage design comprising 3 cohorts: estrogen receptor (ER)-negative (cohort A), ER+ (cohort B1) and ER+ with letrozole (cohort B2). Pts ER+ were randomized to cohorts B1 or B2. The trial included a safety run-in phase of the first 12 pts. For part 1 to be successful, at least 6 pts of 15 had to be progression-free at 6 months (PFS6R of 40%) in each cohort. Secondary objectives included safety and the association of the research-based PAM50 intrinsic subtyping with PFS. PAM50 was performed from FFPE samples using the nCounter platform. Multivariable Cox regression analyses evaluating PAM50 subtypes, age, performance status, treatment line, type of biopsy and endocrine treatment were performed.
Results: A total of 45 pts were recruited (n=15 in each cohort). Median age was 59.5y, and median number of prior lines was 3.0. The PFS6R in cohorts A, B1 and B2 were 33.3% (5/15), 40.0% (6/15) and 53.3% (8/15), respectively. Regarding safety, grade 1-2 and 3-4 toxicities occurred in 97.7% and 84.4% of pts. The most common grade 3-4 toxicities were neutropenia (80%) and thrombocytopenia (17%). Dose reductions were required in 60% of pts. Regarding PAM50, a total of 40 (83.9%) tumors samples (22 primary and 18 metastasis) were profiled. Subtype distribution was as follows: 92.9% HER2-enriched (HER2-E) and 7.1% Basal-like in cohort A, and 46.2% HER2-E, 23.1% Luminal B, 19.2% Luminal A and 11.5% Normal-like in cohorts B1+2. No significant differences in PFS were observed across the 3 cohorts. In cohorts A+B1+B2, Luminal disease defined by PAM50 showed a higher median PFS compared to non-luminal disease (12.4 vs. 4.1 months; adjusted hazard ratio=0.37; p-value=0.052). Clinical Benefit Rate (CBR6) was 73% in Luminal Vs. 31% in non-luminals (p=0.031). In cohorts B1+B2, Luminal disease defined by PAM50 showed a higher median PFS compared to non-luminal disease (12.4 vs. 4.1 months; adjusted hazard ratio=0.30; p-value=0.025). CBR6 was 73% in Luminal Vs. 25% in non-luminals (p=0.022). No clinical-pathological variable was found associated with PFS or CBR6 in all pts or in cohorts B1+B2.
Conclusion: Palbociclib in combination with TTZ is safe and active in TTZ pre-treated HER2+ advanced BC, specially within ER+ disease. Identification of the non-luminal subtypes by PAM50 might help identify pts who might not derive a large benefit from this treatment strategy regardless ER status. Our results might have important implications for current and future clinical trials evaluating CDK4/6 inhibitors in HER2+ disease. In Part 2, a total of 92 pts in cohorts B1 and B2 will be included to better assess the efficacy of this treatment strategy.
Citation Format: Ciruelos E, Villagrasa P, Paré L, Oliveira M, Pernas S, Cortés J, Soberino J, Adamo B, Vazquez S, Martínez N, Perelló A, Bermejo B, Martínez E, Garau I, Melé M, Morales S, Galván P, Pascual T, Canes J, Nuciforo P, Gonzalez X, Prat A. SOLTI-1303 PATRICIA phase II trial (STAGE 1) -- Palbociclib and trastuzumab in postmenopausal patients with HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-03.