In this phase II clinical trial, we evaluated the efficacy of the non-anthracycline combination of carboplatin and nab-paclitaxel in early stage triple negative breast cancer (TNBC).
Patients with newly diagnosed stage II-III TNBC (N=69) were treated with neoadjuvant carboplatin (AUC 6) every 28 days x 4 plus nab-paclitaxel (100 mg/m ) weekly for 16 weeks. Pathological complete response (pCR) and residual cancer burden (RCB) were analyzed with germline mutation status, tumor infiltrating lymphocytes (TILs), TNBC molecular subtype, and GeparSixto immune signature (GSIS).
Sixty-seven patients were evaluable for safety and response. Fifty-three (79%) patients experienced grade 3/4 adverse events (AEs), including Grade 3 anemia (43%), neutropenia (39%), leukopenia (15%), thrombocytopenia (12%), fatigue (7%), peripheral neuropathy (7%), neutropenia (16%), and leukopenia (1%). Twenty-four patients (35%) had at least one dose delay and 50 patients (72%) required dose reduction. Sixty-three (94%) patients completed scheduled treatment. The responses were 32/67 (48%) pCR (RCB 0), 10/67 (15%) RCB I, 19/67 (28%) RCB II, 5/67 (7%) RCB III, and 1/67 (2%) progressed and had no surgery. Univariate analysis showed GSIS “immune-hot” and DNA repair defect (DRD) were associated with higher pCR with odds ratio of 4.62 (P=0.005) and 4.76 (P=0.03) respectively, and with RCB 0/I vs. RCB II/III with odds ratio 4.80 (P=0.01). “Immune-hot” GSIS was highly correlated with DRD status (P=0.03), TILs level (P<0.001), and TNBC molecular subtype (P<0.001). After adjusting for age, race, stage, and grade, GSIS remained associated with higher pCR and RCB class 0/I vs. II/III with odds ratio 7.19 (95% CI 2.01-25.68, P=0.002) and 8.95 (95%. CI 2.09-38.23, P=0.003), respectively.
The combination of carboplatin and nab-paclitaxel for early stage high risk TNBC showed manageable toxicity and encouraging anti-tumor activity. GSIS “immune-hot” signature is associated with higher pCR rate and RCB class 0/1. This study provides additional rationale for using non-anthracycline platinum-based therapy for future neoadjuvant trials in early stage TNBCs.
Platinum is an important neoadjuvant chemotherapy agent for treatment of early stage triple negative breast cancer (TNBC). In this study, carboplatin and nab-paclitaxel were well tolerated and highly effective in TNBC, resulting in pathological complete response of 48%. In univariate and multivariate analyses adjusting for age, race, tumor stage and grade, “immune-hot” GeparSixto Immune Signature (GSIS) and DNA repair defect were associated with higher pCR and residual cancer burden class 0/1. The association of GSIS “immune-hot” signature with higher pCR holds promise for “de-escalating” neoadjuvant chemotherapy for patients with early stage TNBC. Although GSIS is not routinely used in clinic, further development of this immune signature into a clinically applicable assay is indicated.
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