Data from Palbociclib, Trastuzumab, and Endocrine Therapy in Pretreated HER2-Positive and PAM50 Luminal Advanced Breast Cancer: Randomized Phase II, SOLTI-1303 PATRICIA Trial

AbstractPurpose: Based on the results from SOLTI-PATRICIA trial (NCT02448420) cohorts A/B, a direct comparison with standard-of-care treatments is needed to evaluate the efficacy and safety of palbociclib, trastuzumab, and endocrine therapy (ET) in PAM50 luminal A/B pretreated patients. Patients and Methods: SOLTI-PATRICIA cohort C is a randomized, multicenter, prospective, open-label, phase II study. Pretreated patients with HER2-positive, hormone receptor–positive, and PAM50 luminal A/B advanced breast cancer were randomized 1:1 to receive either i) the triplet regimen or ii) trastuzumab-based treatment of physician’s choice (TPC). Patients allocated in the TPC arm were eligible for re-randomization upon disease progression, if the inclusion criteria were still met. The primary endpoint was investigator-assessed progression-free survival (PFS) per RECIST version 1.1. Results: A total of 264 participants were prescreened from August 2019 to 2023, and 73 patients were randomly assigned (including seven re-randomizations). In the TPC arm, 48.5% were treated with trastuzumab plus chemotherapy, 39.4% with trastuzumab emtansine, and 12.1% with trastuzumab plus ET. The triplet was associated with a significantly better PFS compared with TPC [stratified hazard ratio = 0.52; 95% confidence interval (CI), 0.29–0.95; two-sided P = 0.03]. PFS rates after 24 months were 24.0% with the triplet and 4.3% in the TPC arm. The overall response rate was 18.9% (95% CI, 8.6–35.7) and 7.1% (95% CI, 1.2–25.0), respectively. In the triplet arm, grade ≥3 adverse events occurred in 61.5% of patients, with neutropenia being the most frequent (53.9%). No permanent discontinuations due to toxicity were observed. Conclusions: Combining palbociclib, trastuzumab, and ET was safe and significantly improved PFS, compared with TPC, in previously treated patients with HER2-positive, PAM50 luminal A/B advanced breast cancer.