Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis

Alhussein, Muhammad Mustafa; Mokbel, Abir; Cosman, Tammy; Aghel, Nazanin; Yang, Eric H.; Mukherjee, Som D.; Dent, Susan; Ellis, Peter; Dhesy‐Thind, Sukhbinder; Leong, Darryl P.

doi:10.1016/j.cjco.2021.06.019

Cited by 37 publications

(28 citation statements)

References 44 publications

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“…Pertuzumab has been associated with cardiotoxic events, such as heart failure [ 22 ]. To reduce this risk, we excluded participants with a history of or current cardiac disease or left ventricular ejection fraction of ≥ 55% from the study and regularly performed echocardiography and measured blood NT-proBNP concentrations (a biomarker of heart failure) after administration of the study drugs.…”

Section: Discussionmentioning

confidence: 99%

HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) Administered to Healthy Male Subjects

et al. 2022

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Background Pertuzumab is a humanized monoclonal antibody for the treatment of breast cancer. HLX11 is a biosimilar of pertuzumab developed by Shanghai Henlius Biotech, Inc. We conducted a bioequivalence study for HLX11 and pertuzumab (United States [US]-, European Union [EU]-, and China [CN]-approved products). Objectives This study compared the biosimilarity in pharmacokinetics (PK), safety, and immunogenicity between HLX11 and reference pertuzumab (approved in the US, the EU, and CN) in healthy Chinese male participants after a single infusion and further characterized the PK profile of HLX11. Methods Eligible individuals were randomized 1:1:1:1 to receive a single dose of 420 mg HLX11, US-, EU-, or CN-pertuzumab via intravenous infusion over 60 min. The primary endpoints were maximum serum drug concentration ( C max ), area under the serum concentration–time curve (AUC) from time 0 to time of the last quantifiable concentration (AUC 0– t ), and AUC from time 0 to infinity (AUC 0–∞ ). PK bioequivalence was established if the 90% confidence intervals (CIs) of the geometric mean ratios of the primary endpoints were between 80.0 and 125.0%. Secondary endpoints included other PK parameters, safety, and immunogenicity. Results A total of 160 participants were enrolled and randomly assigned to each group ( n = 40 per group). The 90% CIs of the geometric mean ratios of the primary endpoints were all within the prespecified equivalence margins (HLX11 vs. pertuzumab [US-, EU-, CN-approved products]: C max 97.03–115.06%, 91.39–109.80%, 94.53–110.65%; AUC 0– t 87.65–99.68%, 87.07–100.79%, 86.29–101.09%; AUC 0–∞ 87.66–99.90%, 87.54–101.05%, 89.23–103.20%). The incidence of adverse drug reactions was comparable across the four groups. The presence of anti-drug antibodies or neutralizing antibodies had no obvious effect on PK. Conclusion The PK, safety, and immunogenicity of HLX11 were highly similar to those of reference pertuzumab (US-, EU-, CN-approved products). The established bioequivalence supports further clinical trials of HLX11 in cancer treatment. Trial Registration This study was registered with ClinicalTrials.gov (NCT04411550) and Chinadrugtrials.org.cn (CTR20200618). Supplementary Information The online version contains supplementary material available at 10.1007/s40259-022-00534-w.

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Section: Discussionmentioning

confidence: 99%

HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) Administered to Healthy Male Subjects

et al. 2022

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“…Serum HER2 levels are increased in patients with chronic heart failure, and levels correlate inversely with left ventricular function [35]. In an analysis of pooled data from 14 phase II studies ( n = 598), which, in many cases, were nonrandomized, asymptomatic left ventricular systolic dysfunction occurred in 6.9% of patients receiving pertuzumab as monotherapy and in 6.5% of patients receiving the combination of pertuzumab and trastuzumab [36].…”

Section: Discussionmentioning

confidence: 99%

The effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study

Özdemir¹,

Zengel²,

Yıldız

et al. 2022

Anti-Cancer Drugs

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In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

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“…Pertuzumab is a recombinant humanized monoclonal antibody that blocks the HER2 signaling synergically with trastuzumab in early and advanced stages of BC. In a systematic review of phase 2 and 3 randomized controlled trials testing the addiction of pertuzumab in different settings to standard therapies in patients with HER2-positive BC, pertuzumab was associated with no detectable effect on asymptomatic/minimally symptomatic LVD, but the risk of heart failure increases by approximately two-fold [ 70 ].…”

Section: Side Effects Of Systemic Treatmentsmentioning

confidence: 99%

Long-Term Effects of Breast Cancer Therapy and Care: Calm after the Storm?

Tommasi

Balsano

Corianò

et al. 2022

JCM

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Breast cancer is still a lethal disease and the leading cause of death in women, undermining patients’ survival and quality of life. Modern techniques of surgery and radiotherapy allow for the obtaining of good results in terms of survival, however they cause long-term side effects that persist over time, such as lymphedema and neuropathy. Similarly, the advent of new therapies such as endocrine therapy revolutionized breast cancer outcomes, but side effects are still present even in years of follow-up after cure. Besides the side effects of medical and surgical therapy, breast cancer is a real disruption in patients’ lives considering quality of life-related aspects such as the distortion of body image, the psychological consequences of the diagnosis, and the impact on family dynamics. Therefore, the doctor-patient relationship is central to providing the best support both during treatment and afterwards. The aim of this review is to summarize the consequences of medical and surgical treatment on breast cancer patients and to emphasize the importance of early prevention of side effects to improve patients’ quality of life.

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Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis

Cited by 37 publications

References 44 publications

HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) Administered to Healthy Male Subjects

HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) Administered to Healthy Male Subjects

The effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study

Long-Term Effects of Breast Cancer Therapy and Care: Calm after the Storm?

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