A randomized phase III trial of anthracyclines followed by taxane versus taxane plus carboplatin as (neo)adjuvant therapy in patients with triple-negative breast cancer: KCSG BR 15-1 PEARLY trial

BACKGROUND: Platinum agents have been shown to increase pathologic complete response (pCR) rates when added to neoadjuvant chemotherapy for triple-negative breast cancer (TNBC). The PEARLY multicenter, randomized, phase III trial investigated the efficacy and safety of adding carboplatin to standard anthracycline-based and taxane chemotherapy for patients with early-stage TNBC in the neoadjuvant or adjuvant settings. PATIENTS AND METHODS: Patients with stage II or III TNBC were enrolled. Patients received either standard therapy with doxorubicin and cyclophosphamide followed by a taxane (control arm) or carboplatin in addition to a taxane following doxorubicin and cyclophosphamide (carboplatin arm). The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS), invasive disease-free survival (IDFS), distant recurrence-free survival (DRFS), pCR rate, and safety. RESULTS: Between January 2016 and June 2020, 868 patients across 22 institutions in the Republic of Korea were randomly assigned to either the control arm or carboplatin arm. At a median follow-up of 57.2 months, carboplatin significantly improved EFS compared with the control [hazard ratio 0.67, 95% confidence interval (CI) 0.49-0.92, P = 0.012]. The 5-year EFS rates increased from 75.1% to 82.3% with an absolute 7.2% difference. Secondary endpoints, including OS, IDFS, and DRFS, showed directionally consistent trends favoring the carboplatin arm, though none reached statistical significance. Grade 3 or higher treatment-related adverse event rates were more frequent in the carboplatin arm (74.7%) than in the control arm (56.7%), driven primarily by hematologic toxicity. CONCLUSION: The addition of carboplatin to doxorubicin and cyclophosphamide followed by taxane therapy significantly improved EFS in patients with early-stage TNBC. Despite a higher incidence of grade ≥3 adverse events in the carboplatin arm, no clinically meaningful deterioration in quality of life was observed, supporting a favorable risk-benefit profile for carboplatin incorporation into early TNBC treatment.