Anaemia and pathologic complete response rate according to carboplatin dose in HER2+ breast cancer treated with neoadjuvant TCHP

Abstract

Grade 3/4 anaemia, which is mainly induced by carboplatin, frequently occurs in patients treated with neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP). However, dose reduction of carboplatin may raise concerns about the oncological outcome. This study investigated the pathologic complete response (pCR) rate, occurrence of grade 3/4 anaemia, and transfusion rate according to carboplatin dose in patients treated with neoadjuvant TCHP. We retrospectively analysed 294 patients treated with neoadjuvant TCHP between April 2015 and December 2020. Case matching was performed using propensity score matching. Among patients treated with neoadjuvant TCHP, carboplatin area under the plasma concentration-time curve 6 (AUC6) was used in 234 patients (79.6%) and upfront carboplatin AUC5 was used in 60 patients (20.4%). No significant difference in pCR rate was found between the two groups (AUC6: 70.9%, AUC5: 80.0%). In both oestrogen receptor-positive (ER+) and ER- patients, no significant differences were observed between the AUC6 and AUC5 groups (ER+: 54.3% vs. 50.0%, ER-: 81.7% vs. 86.0%). The case-matched cohort showed consistent findings. The AUC5 group had lower frequencies of grade 3/4 anaemia (18.3% vs. 34.2%) and transfusion events (10.0% vs. 21.8%) than the AUC6 group. Compared with AUC5, carboplatin at AUC6 would associate with a 2.7-fold increased risk of grade 3 or 4 chemotherapy-induced anaemia. Carboplatin AUC5 has comparable cytotoxic effects to carboplatin AUC6 in patients with HER2+ breast cancer treated with six cycles of neoadjuvant TCHP, with fewer complications associated with clinically meaningful anaemia. AUC5 may be the optimal carboplatin dose to reduce TCHP-induced anaemia in patients with HER2+ breast cancer treated with TCHP.

Keywords: anaemia; breast cancer; carboplatin; neoadjuvant chemotherapy; pathologic complete response.

FIGURE 1

Pathological complete response (pCR) rates according to carboplatin dose. (A) pCR rates according to carboplatin dose in the whole cohort (N = 294). pCR status according to carboplatin dose was compared using Fisher's exact tests in all patients, in a subset of patients with ER‐HER2+ disease, and in a subset of patients with ER + HER2+ disease (p = 0.159, p = 0.487, and p = 0.793, respectively). (B) pCR rates according to carboplatin dose in the matched cohort (n = 168). pCR status according to carboplatin dose was compared using Fisher's exact tests in all patients, in the ER‐HER2+ subgroup, and in the ER + HER2+ subgroup (p = 0.794, p = 0.672, and p > 0.999, respectively).

FIGURE 2

Distribution of anaemia grade according to carboplatin dose. The proportions of grade 3/4 anaemia according to carboplatin dose were compared using Fisher's exact tests in the (A) whole cohort (N = 294) and (B) matched cohort (n = 168) (p = 0.018 and p = 0.039, respectively).

FIGURE 3

Serial haemoglobin (Hb) levels during neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab treatment according to carboplatin dose. Serial Hb levels according to carboplatin dose were compared using two‐way analysis of variance tests in the (A) whole cohort (N = 294) and (B) matched cohort (n = 168) (p < 0.001 and p < 0.001, respectively).

FIGURE 4

Red blood cell (RBC) transfusion rates according to carboplatin dose. The rates of RBC transfusion according to carboplatin dose were compared using Fisher's exact tests in the (A) whole cohort (N = 294) and (B) matched cohort (n = 168) (p = 0.039 and p = 0.052, respectively).