Carboplatin regimen extends EFS in triple-negative breast cancer

SAN ANTONIO — The addition of carboplatin to sequential taxane-anthracycline neoadjuvant chemotherapy significantly improved outcomes among patients with triple-negative breast cancer, according to study results.

The regimen extended OS and increased pathologic response. The benefit appeared highest among pre- or perimenopausal women aged 50 years or younger, findings presented at San Antonio Breast Cancer Symposium showed.

Background and methods

“A long-standing question in the triple-negative breast cancer space has been whether there is benefit with the addition of platinum chemotherapy in the neoadjuvant or adjuvant setting,” Sudeep Gupta, MBBS, MD, DM, consultant medical oncologist at Tata Memorial Center in Mumbai, India, said during a presentation. “Recent studies have incorporated immune checkpoint inhibitors as part of the chemotherapy backbone, and previous phase 2 studies have suggested an increase in pathologic complete response with the addition of platinum chemotherapy in the neoadjuvant setting. However, these studies were underpowered for survival.”

Gupta and colleagues sought to assess the safety and efficacy of the addition of carboplatin to standard neoadjuvant chemotherapy for triple-negative breast cancer.

The analysis included 717 women (median age, 46 years; 58.3% pre- or perimenopausal; 60.3% locally advanced disease).

Researchers randomly assigned 361 women to area under curve 2 carboplatin plus 100 mg/m² paclitaxel neoadjuvant chemotherapy once weekly for 8 weeks. The other 356 received standard treatment with 100 mg/m² paclitaxel once weekly for 8 weeks, followed by 60 mg/m² doxorubicin or 90 mg/m² epirubicin plus 600 mg/m² cyclophosphamide, once every 21 days for four cycles.

Patients underwent neoadjuvant chemotherapy, followed by surgery for primary tumor and axillary lymph nodes, and then radiotherapy.

EFS served as the primary endpoint. Secondary endpoints included OS and pathologic complete response.

Findings

After median follow-up of 67.6 months, researchers reported a higher 5-year EFS rate with the carboplatin regimen than standard therapy (70.7% vs. 64.1%; HR = 0.79; 95% CI, 0.62-1.02).

Results also showed a higher 5-year OS rate (74.4% vs. 66.8%; HR = 0.74; 95% CI, 0.56-0.96) and a higher pathologic complete response rate (54.5% vs. 40.3%; P < .001) with carboplatin.

“Achievement of pathologic complete response was powerfully prognostic for EFS as well as OS among the overall study population, and [among] both younger and older patients,” Gupta said.

Subgroup analyses showed higher 5-year EFS rates with carboplatin among women aged 50 years or younger (74.2% vs. 61.7%; HR = 0.64; 95% CI, 0.47-0.87), but not among women aged older than 50 years (62% vs. 69.3%; HR = 1.3; 95% CI, 0.82-2.07).

Moreover, researchers observed higher 5-year EFS rates with carboplatin among pre- or perimenopausal women (75% vs. 59.6%; HR = 0.6; 95% CI, 0.43-0.84), but not among post-menopausal women (64.7% vs. 70.5%; HR = 1.19; 95% CI, 0.8-1.78).

“We observed no interactions between EFS and family history, stage, tumor size or clinical nodal status between the groups,” Gupta said.

Researchers observed higher 5-year OS rates with carboplatin among women aged 50 years or younger (77.1% vs. 65.9%; HR = 0.61; 95% CI, 0.44-0.84), but not among women aged older than 50 years (68% vs. 68.9%; HR = 1.13; 95% CI, 0.69-1.83).

Results also showed higher 5-year OS rates with carboplatin among pre- or perimenopausal (78.2% vs. 64.6%; HR = 0.57; 95% CI, 0.39-0.81), but not among post-menopausal women (69% vs. 69.9%; HR = 1.06; 95% CI, 0.7-1.61).

Results showed a higher pathologic complete response rate with carboplatin among women aged 50 years or younger (61% vs. 41.5%; P < .001), but no significant difference among those aged older than 50 years (38.1% vs. 37.5%).

Common grade 3 or higher adverse events that occurred more frequently among carboplatin-treated patients included neutropenia (8.6% vs. 2%), febrile neutropenia (4.4% vs. 2.8%), anemia (1.9% vs. 0.3%) and thrombocytopenia (1.9% vs. 0%).

Treatment compliance and toxicity did not differ substantially between younger and older patients, Gupta said.

Implications

The findings showed the addition of carboplatin to sequential taxane-anthracycline neoadjuvant chemotherapy significantly improved OS and tends to improve EFS among patients with operable and locally advanced triple-negative breast cancer, Gupta said.

“The precise reasons for interaction between age and menopausal status and carboplatin are unclear,” he added.