Palbociclib, trastuzumab and endocrine therapy in pretreated HER2-positive and PAM50 luminal advanced breast cancer: randomised phase II, SOLTI-1303 PATRICIA trial

Purpose: 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 randomised, multicentre, prospective, open-label, phase II study. Pretreated patients with HER2-positive, HR-positive, and PAM50-Luminal A/B ABC were randomised 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 1.1. Results: 264 participants were pre-screened between August 2019-2023, and 73 patients were randomised (including seven re-randomisations). In the TPC arm: 48.5% were treated with trastuzumab plus chemotherapy, 39.4% with T-DM1 and 12.1 % with trastuzumab plus ET. The triplet was associated with a significantly better PFS compared to TPC (stratified hazard ratio=0.52 [95% 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 improved significantly PFS, compared to TPC in previously treated HER2-positive, PAM50 luminal A/B ABC patients.