Dataset Information

Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer.

ABSTRACT:

Purpose

Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH.

Methods

We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis were used for statistical analysis.

Results

In this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation.

Conclusions

Pertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.

SUBMITTER: Spring L

PROVIDER: S-EPMC6235701 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer.

Spring Laura L Niemierko Andrzej A Haddad Stephanie S Yuen Megan M Comander Amy A Reynolds Kerry K Shin Jennifer J Bahn Atul A Brachtel Elena E Specht Michelle M Smith Barbara L BL Taghian Alphonse A Jimenez Rachel R Peppercorn Jeffrey J Isakoff Steven J SJ Moy Beverly B Bardia Aditya A

Breast cancer research and treatment 20180915 3

<h4>Purpose</h4>Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH ...[more]

PMID: 30220055

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Project description:BackgroundThe introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab.MethodsFrom a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups.ResultsBluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36-4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25-0.80) and BCSS (aHR 0.46, 95% CI 0.24-0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes.ConclusionsIn patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.

Project description:BackgroundIn patients with metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (HER2), progression-free survival was significantly improved after first-line therapy with pertuzumab, trastuzumab, and docetaxel, as compared with placebo, trastuzumab, and docetaxel. Overall survival was significantly improved with pertuzumab in an interim analysis without the median being reached. We report final prespecified overall survival results with a median follow-up of 50 months.MethodsWe randomly assigned patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for their metastatic disease to receive the pertuzumab combination or the placebo combination. The secondary end points of overall survival, investigator-assessed progression-free survival, independently assessed duration of response, and safety are reported. Sensitivity analyses were adjusted for patients who crossed over from placebo to pertuzumab after the interim analysis.ResultsThe median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months. This analysis was not adjusted for crossover to the pertuzumab group and is therefore conservative. Results of sensitivity analyses after adjustment for crossover were consistent. Median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (hazard ratio, 0.68; 95% CI, 0.58 to 0.80). Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained.ConclusionsIn patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this drug combination. (Funded by F. Hoffmann-La Roche and Genentech; CLEOPATRA ClinicalTrials.gov number, NCT00567190.).

Dataset Information

Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer.

Purpose

Methods

Results

Conclusions

Publications

Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer.

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