Triple-negative breast cancer (TNBC) is known to be associated with a high risk of early relapse and poor prognosis.¹ TNBC cells are susceptible to platinum-based chemotherapy due to frequent genomic instabilities and deficiencies in DNA repair mechanisms.¹ Integration of carboplatin into neoadjuvant therapy has thus been incorporated into standard practice for early TNBC based on results showing enhanced pathological complete response (pCR).¹ However, evidence regarding the survival benefit of platinum in early TNBC remains inconclusive.¹ During the 2024 ASCO Annual Meeting, Dr. Joohyuk Sohn from the Yonsei Cancer Center, South Korea, presented findings of the multicenter, randomized, open-label phase 3 PEARLY trial, which the Korean Cancer Study Group conducted to assess the efficacy and safety of carboplatin in combination with anthracycline/taxane therapy compared to standard anthracycline/taxane alone as neoadjuvant or adjuvant treatment in early-stage TNBC.¹

In this trial, 868 patients with stage II or III TNBC were enrolled and randomly assigned 1:1 to the control arm (n=434) or the carboplatin arm (n=434).¹ All patients had a tumor size ≥2cm and were stratified by institution, nodal status, BRCA status, and treatment setting (neoadjuvant or adjuvant).¹ In the control arm, patients received 4 cycles of the AC regimen (doxorubicin and cyclophosphamide), followed by 4 cycles of taxane (paclitaxel or docetaxel).¹ In the experimental arm, patients received carboplatin in addition to taxane for 4 cycles following AC.¹ The primary endpoint of the trial was the 5-year event-free survival (EFS), defined as disease progression or inoperable status for the neoadjuvant group, local or distant recurrence, occurrence of a second primary cancer, or death from any cause.¹ The secondary endpoints included overall survival (OS), distant recurrence-free survival (DRFS), invasive disease-free survival (IDFS), pCR, safety, and quality of life (QoL).¹

At a median follow-up of 57.2 months, the carboplatin arm showed significantly improved EFS with a 5-year EFS rate of 82.3% compared with 75.1% in the control arm (HR=0.67; 95% CI: 0.49-0.92; p=0.012).¹ The carboplatin arm showed a reduced total number of events (15.7% vs. 21.9%), including progression during neoadjuvant therapy (4.2% vs. 8.9%), and local (1.8% vs. 3.2%) and distant recurrence (8.8% vs. 10.4%).¹ Subgroup analysis showed similar benefits with carboplatin addition regardless of subgroup categories such as nodal status, tumor stage, treatment setting, and BRCA status.¹

For the secondary endpoints, the 5-year OS rate was 90.7% in the carboplatin arm and 87.0% in the control arm (HR=0.65; 95% CI: 0.42-1.02; p=0.057), however, the data were immature and further follow-up is needed.¹ Both IDFS (HR=0.73; 95% CI: 0.52-1.02; p=0.07) and DRFS (HR=0.77; 95% CI: 0.52-1.12; p=0.17) favored the carboplatin arm but the difference was not statistically significant.¹ In the neoadjuvant setting, pCR was achieved in 46.0% of patients in the carboplatin arm compared with 39.4% in the control arm.¹ pCR was also a strong prognostic factor for EFS (pCR vs. non-PCR HR=0.16; 95% CI: 0.10-0.27; p<0.0001).¹

Safety profiles of both arms were consistent with previous studies, but treatment-related adverse events were more frequent in the carboplatin arm including hematologic and non-hematologic events.¹ Serious adverse events were reported in 16.4% in the carboplatin arm and 14.1% in the control arm, and events leading to dose reduction or permanent discontinuation were also more common in the carboplatin arm.¹ QoL scores were not significantly different between the 2 groups.¹

In summary, the addition of carboplatin to standard anthracycline followed by taxane therapy significantly improved EFS in patients with early-stage TNBC.¹ The safety profile was consistent with the known expectations for each regimen and no difference in QoL between the two groups was found.¹ This provides compelling evidence to support the inclusion of carboplatin in the treatment of early-stage TNBC in both the neoadjuvant and adjuvant settings post-surgery.¹