Safety and efficacy analysis of neoadjuvant pertuzumab, trastuzumab and standard chemotherapy for HER2-positive early breast cancer: real-world data from NeoPowER study

Abstract

Background: The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has shown to increase the pathological complete response (pCR) rate, without main safety concerns. The aim of NeoPowER trial is to evaluate safety and efficacy of P + H + CT in a real-world population.

Methods: We retrospectively reviewed the medical records of stage II-III, HER2 + BC patients treated with NaT: who received P + H + CT (neopower group) in 5 Emilia Romagna institutions were compared with an historical group who received H + CT (control group). The primary endpoint was the safety, secondary endpoints were pCR rate, DRFS and OS and their correlation to NaT and other potential variables.

Results: 260 patients were included, 48% received P + H + CT, of whom 44% was given anthraciclynes as part of CT, compared to 83% in the control group. The toxicity profile was similar, excluding diarrhea more frequent in the neopower group (20% vs. 9%). Three patients experienced significant reductions in left ventricular ejection fraction (LVEF), all receiving anthracyclines. The pCR rate was 46% (P + H + CT) and 40% (H + CT) (p = 0.39). The addition of P had statistically correlation with pCR only in the patients receiving anthra-free regimens (OR = 3.05,p = 0.047). Preoperative use of anthracyclines (OR = 1.81,p = 0.03) and duration of NaT (OR = 1.18,p = 0.02) were statistically related to pCR. 12/21 distant-relapse events and 14/17 deaths occurred in the control group. Patients who achieve pCR had a significant increase in DRFS (HR = 0.23,p = 0.009).

Conclusions: Adding neoadjuvant P to H and CT is safe. With the exception of diarrhea, rate of adverse events of grade > 2 did not differ between the two groups. P did not increase the cardiotoxicity when added to H + CT, nevertheless in our population all cardiac events occurred in patients who received anthracycline-containing regimens. Not statistically significant, higher pCR rate is achievable in patients receiving neoadjuvant P + H + CT. The study did not show a statistically significant correlation between the addition of P and long-term outcomes.

Keywords: Early breast cancer; HER2 dual blockade; HER2+; Neoadjuvant treatment; Pertuzumab; Real world data.

Fig. 1

Overall AEs in P + H + CT and H + CT groups

Fig. 2

(a) Patients’ cardiovascular risk factors (CVRF) at diagnosis, distributed according to the treatment arm and the use of neoadjuvant anthracycline. (b) Number of CVRF per patient at diagnosis, distributed according to the treatment arm and the use of neoadjuvant anthracycline

Fig. 3

(a) Patients’ concomitant cardiovascular drugs at diagnosis, distributed according to the treatment arm and the use of neoadjuvant anthracycline. (b) Number of concomitant cardiovascular drugs per patient at diagnosis, distributed according to the treatment arm and the use of neoadjuvant anthracycline

Fig. 4

change in LVEF after neoadjuvant: (a) P + H + CT, Anthra YES; (b) P + H + CT, Anthra NO; (c) H + CT, Anthra YES; (d) H + CT, Anthra NO

Fig. 5

Differences in pCR rate in overall population according to statistically significant variables and treatment arm

Fig. 6

(a) Kaplan Meier curves for distant relapse free survival – DRFS; (b) Forest plot representing Cox proportional hazard model adjusted for unbalanced parameters related to DRFS (Neopower vs. Control)

Fig. 7

(a) Kaplan Meier curves for overall survival - OS; (b) Forest plot representing Cox proportional hazard model adjusted for unbalanced parameters related to OS (Neopower vs. Control)

Fig. 8

Kaplan Meier curves for distant relapse free survival – DRFS (pCR vs. no-pCR)

Fig. 9

Kaplan Meier curves for overall survival – OS (pCR vs. no-pCR)