Palbociclib Combination Is Safe, Efficacious in Patients With HER2-Positive Metastatic Breast Cancer

Palbociclib (Ibrance; Pfizer) plus trastuzumab (Herceptin; Genentech Inc ) and endocrine therapy (ET) yielded favorable survival outcomes and safety in patients with HER2-positive, PAM50 luminal A/B advanced breast cancer. The results are from the randomized, multicenter, prospective, open-label, phase 3 SOLTI-PATRICIA trial (NCT02448420).¹

Breast Cancer Subtypes and Statistics

Breast cancer is the most common cancer in women, accounting for 30% of all new diagnoses in female patients. Treatment of breast cancer has evolved drastically alongside the discovery of biomarkers and subtypes, enhancing the development and clinical efficacy of modern therapies.²

Of the subtypes, hormone receptor-positive (HR+)/HER2-negative (HER2–) breast cancer is the most prevalent, representing about 70% of all cases. Other subtypes include HR-negative (HR–)/HER2–, HR+/HER2-positive (HER2+), and HR–/HER2+ breast cancer.³

HER2 alterations are well-established drivers of disease and are associated with higher risk of recurrence and poor therapeutic response. There are various available treatments—both approved and investigational—for patients with HER2-altered breast cancers, such as HER2-targeted therapies, CDK4/6 inhibitors, and ET.³

The Phase 3 SOLTI-PATRICIA Trial

In the SOLTI-PATRICIA trial, investigators assessed a therapeutic regimen that included palbociclib, trastuzumab, and letrozole (Femara; Novartis) as the ET. The study included a total of 264 participants with HR–/HER2+ and HR+/HER2+ breast cancer who were randomized 1:1 to 1 of 3 cohorts detailed in the Table below.⁴

The primary end point of the study was investigator-assessed progression-free survival (PFS) evaluated according to RECIST 1.1 criteria. Between August 2019 and 2023, a total of 264 participants were pre-screened, and 73 patients were ultimately randomized, including seven who were re-randomized. In the treatment of physician’s choice (TPC) arm, 48.5% of patients received trastuzumab plus chemotherapy, 39.4% received (T-DM1, Kadcyla; Genentech), and 12.1% received trastuzumab combined with ET.⁴

The triplet regimen demonstrated a significantly longer PFS compared with TPC, with a stratified hazard ratio of 0.52 (95% CI, 0.29–0.95; 2-sided P = 0.03). At 24 months, PFS rates were 24.0% with the triplet and 4.3% with TPC. The overall response rate was 18.9% (95% CI, 8.6–35.7) for the triplet regimen and 7.1% (95% CI, 1.2–25.0) for TPC.⁴

Grade 3 or greater adverse events occurred in 61.5% of patients receiving the triplet, with neutropenia reported most frequently (53.9%). Importantly, no patients discontinued therapy permanently due to toxicity.⁴

These findings indicate that the combination of palbociclib, trastuzumab, and ET was well tolerated and resulted in a significant improvement in PFS compared with TPC in previously treated patients with HER2-positive, PAM50 luminal A/B advanced breast cancer.

REFERENCES

1. Study of palbociclib and trastuzumab with endocrine therapy in HER2-positive metastatic breast cancer (PATRICIA II). Clinicaltrials.gov. Updated April 18, 2024. Accessed December 4, 2025. https://clinicaltrials.gov/study/NCT02448420#study-overview

2. Key Statistics for Breast Cancer. American Cancer Society. Updated May 5, 2025. Accessed December 4, 2025. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html

3. Cancer stat facts: female breast cancer subtypes. National Cancer Institute. Accessed December 4, 2025. https://seer.cancer.gov/statfacts/html/breast-subtypes.html

4. Ciruelos E, Pascual T. Villacampa G, et al. Palbociclib, trastuzumab and endocrine therapy in pretreated HER2-positive and PAM50 luminal advanced breast cancer: randomised phase II, SOLTI-1303 PATRICIA trial. Clin Cancer Res (2025). December 3, 2025. Doi:10.1158/1078-0432.CCR-25-2882