Palbociclib and trastuzumab in HER2-positive advanced breast cancer: Results from the phase II SOLTI-1303 PATRICIA trial.

Ciruelos, Eva M; Villagrasa, Patricia; Pascual, Tomás; Oliveira, Mafalda; Pernas, Sonia; Paré, Laia; Escrivá-de-Romaní, Santiago; Manso, Luis; Adamo, Barbara; Martínez de Dueñas, Eduardo; Cortés, Javier; Vázquez, Silvia; Perelló, Antonia; Garau, Isabel; Melé, Mireia; Martínez Jañez, Noelia; Montaño, Alvaro; Bermejo, Begoña; Morales, Serafín; Echarri, Mª Jose; Vega, Estela; González-Farré, Blanca; Martínez, Débora; Galván, Patricia; Canes, Jordi; Nuciforo, Paolo; Gonzà lez Farré, Xavier; Prat, Aleix

PURPOSE To assess palbociclib in combination with trastuzumab with or without endocrine therapy in patients with HER2-positive advanced breast cancer. PATIENTS AND 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 2-stage design comprising 3 cohorts: estrogen receptor (ER)-negative (cohort A), ER-positive (cohort B1) and ER-positive with letrozole (cohort B2). ER-positive patients were randomized to cohorts B1 or B2. Primary endpoint was progression-free survival rate at 6 months (PFS6). Secondary objectives included safety and evaluation of the PAM50 intrinsic subtypes. RESULTS 71 patients were recruited (n=15 in cohort A and 28 in each cohort B). The PFS6 rate in cohorts A, B1 and B2 was 33.3% (5/15), 42.8% (12/28) and 46.4% (13/28), respectively. Regarding safety, grade 1-2 and 3-4 toxicities occurred in 97.7% and 84.4% of patients, respectively. The most common grade 3-4 toxicities were neutropenia (66.4%) and thrombocytopenia (11.3%). Regarding PAM50, 59 (83.1%) tumors were profiled. Luminal disease defined by PAM50 was found independently associated with longer PFS compared to non-luminal disease (10.6 vs. 4.2 months median PFS; adjusted hazard ratio=0.40; p-value=0.003). CONCLUSION Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pre-treated ER-positive/HER2-positive advanced breast cancer with a PAM50 luminal A or B subtype. The enrollment was stopped prematurely and a new randomized cohort was opened in this population.