Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting

Abstract

We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression-free survival at first-line (mPFS1) was 12 months. Pertuzumab as first-line conferred longer mPFS1 compared to other first-line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second-line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T-DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs-negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T-DM1 in second-line after pertuzumab were significantly lower compared to pertuzumab-naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment-related outcomes of HER2-positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2-positive (mbc) patients.

Keywords: HER2 positive; T-DM1; advanced breast cancer; pertuzumab; real world; trastuzumab.

Figure 1

First line and second line of patients divided according to if they received pertuzumab or not in first‐line and T‐DM1 or not in the second‐line. Correlation between sequences of treatment and 3 years OS rate of patients, divided according to immunohistochemistry subtype. Abbreviations: ER, estrogen receptor; HRS, hormone receptors; OS, overall survival; P, pertuzumab; PFS, progression‐free survival; PR, progesterone receptor; P based regimen, pertuzumab‐based regimen; P Yes I, received pertuzumab in first‐line; T‐DM1 Yes II, received T‐DM1 in second‐line; P No I, did not a pertuzumab‐based regimen in first‐line; T‐DM1 No II, did not receive T‐DM1 in second‐line.

Figure 2

The comparison of progression‐free survival in the first‐line of treatment (PFS1) between patients that received a pertuzumab‐based regimen (Pert) and those who did not (No Pert) in the overall population (a), in triple‐positive patients (b), in Er‐ or PgR‐positive patients (c) and in HRs‐negative patients (d). Abbreviations: Er, estrogen receptor; PgR, progesterone receptor; HRs, hormone receptors.

Figure 3

The comparison of overall survival (OS) between patients that did not receive a pertuzumab‐based regimen in first‐line and did not receive T‐DM1 as a second‐line of treatment (No/No, red color), patients that did not receive a pertuzumab‐based regimen in first‐line and received T‐DM1 as a second‐line of treatment (No/Yes, green color), patients that received a pertuzumab‐based regimen in first‐line and T‐DM1 as a second‐line of treatment (Yes/Yes, gray color) and those who received a pertuzumab‐based regimen in first‐line and did not receive T‐DM1 as a second‐line of treatment (Yes/No, blue color). The comparison was done in the overall population (a), in triple‐positive patients (b), in Er o PgR positive patients (c) and in HRs negative patients (d). The adjacent percentages to each survival curve refer to the 3‐year survival rate.