Pertuzumab-associated diarrhea in HER2/neu-positive breast cancer patients: A comparison of trials to actual practice

Background Although landmark trials in the metastatic (CLEOPATRA) and neo-adjuvant (NeoSphere; TRYPHAENA) settings identified all-grade diarrhea as a pertuzumab-associated adverse event, it was not classified as dose-limiting. In actual practice, diarrhea is often a reason for treatment modifications. Objectives To compare the risk of pertuzumab-associated diarrhea in actual practice to the risks in randomized controlled trials. Methods We conducted a retrospective cohort study of HER2/neu-positive breast cancer patients who received a pertuzumab-containing regimen between January 2012 and August 2015. We calculated the risk of diarrhea with 95% confidence limits (CLs), and then used two-sample t-tests to compare the risk between trials and actual practice. Results A total of 27 patients in the study cohort received a pertuzumab-containing treatment regimen for HER2/neu-positive breast cancer. The overall risk of all-grade and severe diarrhea in actual practice was 70% (95% CLs 55–90%) and 37% (95% CLs 20–66%), respectively. No severe diarrhea was observed in the metastatic setting, and the risk of all-grade diarrhea (44%, 95% CLs 21–92%) was similar to the CLEOPATRA study (67%). The risk of all-grade diarrhea in the neo-adjuvant setting was 83% (95% CLs 68–100%), compared to 46% in the NeoSphere trial (p = 0.03). The risk of severe diarrhea (Grade 3–4) in the neo-adjuvant setting was 47% (95% CLs 27–80%) versus 6% in the NeoSphere (p < 0.0001) and 12% in the TRYPHAENA (p < 0.01) trials. Conclusions The risk of all-grade and severe diarrhea associated with neoadjuvant pertuzumab use for HER2/neu-positive breast cancer was greater in actual practice than in trials.

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Safety and efficacy of the HER2-derived GP2 peptide vaccine in combination with trastuzumab for breast cancer patients in the adjuvant setting.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.3096 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 3096-3096

Author(s):

Ritesh Patil ◽

Guy T. Clifton ◽

Jennifer Keating Litton ◽

Nathan M. Shumway ◽

Timothy J Vreeland ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Peptide Vaccine ◽

In Vitro Assays ◽

Breast Cancer Patients ◽

Adjuvant Setting ◽

Cardiac Events ◽

Specific Ctls ◽

Grade 3

3096 Background: GP2 is a 9 amino acid HLA-A2/A3 restricted HER2-derived peptide. GP2 + GM-CSF has been shown to be safe and effective in eliciting anti-HER2 immune response in breast cancer patients. Preclinical data has demonstrated that pretreatment of cells with trastuzumab (Tz) enhances susceptibility to lysis by GP2-specific cytotoxic T lymphocytes (CTLs). We conducted a phase Ib study to evaluate the combination of the GP2 vaccine and Tz. Methods: HLA-A2/A3 + patients with HER2 overexpressing breast cancer receiving Tz as standard therapy were enrolled. The study was designed as a 3+3 dose escalation trial with an expansion cohort evaluating 4 dose levels of the vaccine administered as 6 inoculations given every 3 weeks in combination with Tz (6mg/kg). Toxicity was graded 48-72 hr post vaccination using NCI Toxicity Criteria. Ejection fraction (EF) was monitored every 3 mo. Immunologic response was assessed in vivo by injection site local reaction (LR) and in vitro by quantifying the number of GP2-specific CTLs by HLA-A2: IgG dimer assays and their functional activity by ELISPOT. Results: 19 patients enrolled (median age 47 yr, mean tumor size 3.4 cm, 74% were grade 3, 53% ER/PR+, 63% node positive, 74% received anthracycline based therapy). Maximum local toxicities were grade 1 (77% of patients) and grade 2 (6%), and maximum systemic toxicities were grade 1 (24%) and grade 2 (5%). There were no grade 3 or 4 local or systemic toxicities. There was no significant change in EF at 3 mo (57± 1%, p=0.23) or 6 mo (59±1%, p=0.8) compared to baseline (58±0.9%). Mean post-vaccine series LR was significantly larger than initial vaccination LR (68.2 ± 8.6 mm vs 28.0 ± 10.3 mm, p=0.0004). In vitro assays demonstrated an increase in the maximal number of post- versus pre-vaccination GP2-specific CTLs by dimer assay (1.45 ± 0.19 vs 0.96 ± 0.19%, p=0.06) and increased ELISPOT activity [median 86 range (3-194) vs 34 (range 0-295) spots/106 cells]. Conclusions: GP2 vaccine in combination with Tz is both safe and immunogenic in HER2-overexpressing breast cancer patients in the adjuvant setting. Toxicity was limited to mild local and systemic reactions. There were no dose limiting toxicities or cardiac events.

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ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy

OncoTargets and Therapy ◽

10.2147/ott.s142698 ◽

2017 ◽

Vol Volume 10 ◽

pp. 4859-4867 ◽

Cited By ~ 6

Author(s):

Fangbin Song ◽

Jianbing Zhang ◽

Shanbao Li ◽

Junyi Wu ◽

Tao Jin ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Patients ◽

Endocrine Therapy ◽

Late Recurrence ◽

Adjuvant Endocrine Therapy ◽

Breast Cancer Patients ◽

Er Positive ◽

Grade 3 ◽

Positive Breast Cancer

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Safety and clinical evaluation of dual inhibition with pertuzumab and trastuzumab in HER-2-positive breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12520 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12520-e12520

Author(s):

Christoph Suppan ◽

Daniel Steiner ◽

Valentina Eva Klocker ◽

Florian Posch ◽

Elisabeth Christina Henzinger ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Stage ◽

Local Relapse ◽

Continuous Variables ◽

Breast Cancer Patients ◽

Safety And Efficacy ◽

Metastatic Setting ◽

Her 2 ◽

Positive Breast Cancer

e12520 Background: The addition of Herceptin to standard chemotherapy improved survival in patients with Her-2-positive breast cancer in neoadjuvant, adjuvant and metastatic setting. In higher tumor stage, the addition of pertuzumab is now standard of care and associated with a favorable toxicity profile. The purpose of this study was to evaluate the safety and efficacy of the biosimilar trastuzumab-dttb in combination with pertuzumab in Her-2-positive breast cancer patients. Methods: Thirty-five female patients with Her-2-positive breast cancer treated at the Division of Oncology at the Medical University of Graz between September 2018 and August 2019 were included. Summary measures are reported as medians 25th– 75thpercentile for continuous variables and as absolute frequencies (%) for count data. Results: Thirty-five patients received a median of four [3-7] cycles of trastuzumab-dttb plus pertuzumab. The median cumulative trastuzumab-dttb dose was 1904mg [1560-2640] and the median cumulative pertuzumab dose was 2100mg [1680-3360]. All patients had a normal baseline LVEF (> 50%) prior to the initiation of trastuzumab-dttb plus pertuzumab treatment with a median LVEF of 60% [60-65]. At completion of trastuzumab-dttb plus pertuzumab treatment (or in case of ongoing therapy the last EF assessment), the median LVEF was 60.0 % [58-62]. 21 patients had a median absolute LVEF decline of 1% -5-0], corresponding to a median percent change of 1.7 percent points [-7.7-0]. Two patients (5.7%) had a LVEF reduction ≤50%. None of the patients had a decline in LVEF of ≥ 10 %. In 8 patients, a switch from Herceptin to trastuzumab-dttb was tolerated well and these were also included in the analyses. In only two palliative patients, pertuzumab was either interrupted or stopped due to diarrhea and appetite loss, while trastuzumab-dttb was ongoing. 24 of 35 patients (69%) were treated with trastuzumab-dttb plus pertuzumab in the neoadjuvant setting. Two of these patients were treated for local relapse and were excluded for efficacy assessment. Of the remaining 22 patients, 11 patients achieved a pCR (ypT0/ypTis and ypN0). Conclusions: In these series of Her-2-positive breast cancer patients, the combination of trastuzumab-dttb/pertuzumab was consistent with the known safety and efficacy profile of Herceptin/pertuzumab.

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Quantitative HER2 homodimer levels correlate with time to first recurrence in HER2-positive breast cancer patients who did not receive trastuzumab in the adjuvant setting.

10.1158/0008-5472.sabcs-1074 ◽

2009 ◽

Author(s):

M Bates ◽

W Koestler ◽

E Fuchs ◽

J Sperinde ◽

K Leitzel ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Adjuvant Setting ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

First Recurrence ◽

Positive Breast Cancer

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Dose-Dense Epirubicin and Cyclophosphamide Followed by Weekly Paclitaxel in Node-Positive Breast Cancer

Chemotherapy Research and Practice ◽

10.1155/2014/259312 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6

Author(s):

Hamid Reza Mirzaei ◽

Fatemeh Nasrollahi ◽

Ladan Mohammadi Yeganeh ◽

Sepideh Jafari Naeini ◽

Pegah Bikdeli ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Weekly Paclitaxel ◽

Hematologic Toxicity ◽

Breast Cancer Patients ◽

Node Positive ◽

Grade 3 ◽

Dose Dense ◽

Positive Breast Cancer

Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement in node-positive breast cancer patients but the optimal dose schedule has still remained undetermined. Objectives. The feasibility of dose-dense epirubicin in combination with cyclophosphamide (EC) followed by weekly paclitaxel as adjuvant chemotherapy in node-positive breast cancer patients was investigated. Methods. All patients were treated with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) every two weeks for four cycles with daily Pegfilgrastim (G-CSF) that was administered 3–10 days after each cycle of epirubicin and cyclophosphamide infusion which followed by (80 mg/m2) paclitaxel for twelve consecutive weeks. Results. Sixty consecutive patients were analyzed, of whom 57 patients (95%) completed the regimen and no case of toxicity-related death was observed. Grade 3/4 hematologic toxicity was uncommon and the most common grade 3/4 nonhematological adverse event was neuropathy disorders. Conclusions. Dose-dense epirubicin and cyclophosphamide followed by weekly paclitaxel with G-CSF support is a well-tolerated and feasible regimen in node-positive breast cancer patients without serious complications.

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