Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial

Azambuja, Evandro de; Agostinetto, Elisa; Procter, Marion; Eiger, Daniel; Pondé, Noam; Guillaume, Sébastien; Parlier, Damien; Lambertini, Matteo; Desmet, A.; Caballero, Carmela; Aguila, C.; Jérusalem, Guy; Walshe, Janice; Frank, Elizabeth S.; Bines, José; Loibl, Sibylle; Piccart‐Gebhart, Martine; Ewer, Michael S.; Dent, Susan; Plummer, Chris; Suter, Thomas M.

doi:10.1016/j.esmoop.2022.100772

Cited by 10 publications

(6 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study reported that 8.6% of HER2-positive breast cancer patients undergoing dual anti-HER2 therapy experienced cardiotoxicity (Huang et al, 2022), and another study reported that the rate of cardiotoxicity was 2.0%-6.5% under dual anti-HER2 therapy (Swain et al, 2018). Interestingly, a recent large-scale study involving 4,769 HER2-positive breast cancer patients revealed that 3.3% of patients experienced cardiotoxicity during dual anti-HER2 therapy (de Azambuja et al, 2023). The current study revealed that 6.8% of HER2-positive breast cancer patients experienced cardiotoxicity during neoadjuvant dual anti-HER2 therapy, which was within the range of cardiotoxicity reported in previous studies (Mantarro et al, 2016;Schneeweiss et al, 2018;Swain et al, 2018;Al-Saleh et al, 2022;Huang et al, 2022;de Azambuja et al, 2023).…”

Section: Discussionsupporting

confidence: 85%

“…Interestingly, a recent large-scale study involving 4,769 HER2-positive breast cancer patients revealed that 3.3% of patients experienced cardiotoxicity during dual anti-HER2 therapy (de Azambuja et al, 2023). The current study revealed that 6.8% of HER2-positive breast cancer patients experienced cardiotoxicity during neoadjuvant dual anti-HER2 therapy, which was within the range of cardiotoxicity reported in previous studies (Mantarro et al, 2016;Schneeweiss et al, 2018;Swain et al, 2018;Al-Saleh et al, 2022;Huang et al, 2022;de Azambuja et al, 2023). However, the rate of cardiotoxicity in the current study was slightly greater than the average reported by previous studies.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

GDF-15 is a potential candidate biomarker for an elevated risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy

Tian,

Zhang,

Liu

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

ObjectiveGrowth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that regulates myocardial injury, cardiac overloading pressure, and inflammation and is related to the risk of cardiovascular diseases and events. The current study aimed to investigate the correlation of GDF-15 levels with clinical features, biochemical indices, and especially the risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.MethodsA total of 103 HER2-positive breast cancer patients who underwent neoadjuvant dual anti-HER2 therapy (trastuzumab and pertuzumab plus chemotherapy) were included. Serum GDF-15 levels before neoadjuvant treatment were detected by enzyme-linked immunosorbent assay. Cardiotoxicity was evaluated during neoadjuvant therapy by referring to a decline of ≥10 percentage points in the left ventricular ejection fraction from baseline to an absolute level less than 50%.ResultsGDF-15 exhibited a skewed distribution, with a median level of 714 (range: 207–1805) pg/mL. GDF-15 was positively correlated with age (p = 0.037), diabetes (p = 0.036), and the N-terminal pro-brain natriuretic peptide level (p = 0.013) and positively correlated with the total cholesterol level (p = 0.086) and troponin T level (p = 0.082), but these correlations were not statistically significant. A total of 6.8% of patients experienced cardiotoxicity during neoadjuvant therapy. By comparison, the GDF-15 level was greater in patients who experienced cardiotoxicity than in those who did not (p = 0.008). A subsequent receiver operating characteristic curve revealed that GDF-15 predicted cardiotoxicity risk, with an area under the curve of 0.803 (95% CI: 0.664–0.939). After multivariate adjustment, GDF-15 independently predicted a greater risk of cardiotoxicity (p = 0.020).ConclusionGDF-15 is a candidate biomarker for increased risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

GDF-15 is a potential candidate biomarker for an elevated risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy

Tian,

Zhang,

Liu

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…This is to protect patients undergoing new and effective anti-HER2 therapies that increase both survival and exposure to potentially toxic drugs. Specifically, overall cardiotoxicity profile of dual HER2 blockade is safe [ 28 ]. However, a recently reported pooled analysis showed that dual blockade with pertuzumab was associated with an increased risk of heart failure compared with trastuzumab (Relative Risk = 4.18, 95% Confidence Interval: 1.07–16.30) [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNAs and therapy-associated cardiac events in HER2-positive breast cancer patients: an exploratory analysis from NeoALTTO

Pizzamiglio,

Ciniselli,

de Azambuja

et al. 2024

Breast Cancer Res Treat

Self Cite

View full text Add to dashboard Cite

Purpose The relevance of cardiotoxicity in the context of HER2-positive breast cancer is likely to increase with increasing patient treatment exposure, number of treatment lines, and prolonged survival. Circulating biomarkers to early identify patients at risk of cardiotoxicity could allow personalized treatment and follow-up measures. The aim of this study is to examine the relationship between circulating microRNAs and adverse cardiac events in HER2-positive breast cancer patients. Methods We based our work on plasma samples from NeoALTTO trial obtained at baseline, after 2 weeks of anti-HER2 therapy, and immediately before surgery. Eleven patients experienced either a symptomatic or asymptomatic cardiac event. Circulating microRNAs were profiled in all patients presenting a cardiac event (case) and in an equal number of matched patients free of reported cardiac events (controls) using microRNA-Ready-to-Use PCR (Human panel I + II). Sensitivity analyses were performed by increasing the number of controls to 1:2 and 1:3. Normalized microRNA expression levels were compared between cases and controls using the non-parametric Kruskal–Wallis test. Results Eight circulating microRNAs resulted differentially expressed after 2 weeks of anti-HER2 therapy between patients experiencing or not a cardiac event. Specifically, the expression of miR-125b-5p, miR-409-3p, miR-15a-5p, miR-423-5p, miR-148a-3p, miR-99a-5p, and miR-320b increased in plasma of cases as compared to controls, while the expression of miR-642a-5p decreases. Functional enrichment analysis revealed that all these microRNAs were involved in cardiomyocyte adrenergic signaling pathway. Conclusion This study provides proof of concept that circulating microRNAs tested soon after treatment start could serve as biomarkers of cardiotoxicity in a very early stage in breast cancer patients receiving anti-HER2 therapy.

show abstract

“…Regarding potential safety concerns, in the phase 3 APHINITY trial ( n = 4769) [ 13 ], dual blockade with trastuzumab + pertuzumab (HP) was found to carry no greater cardiac risk than trastuzumab alone (incidence of cardiac events: 3.5% versus 3.2%, respectively). Anthracycline use was associated with increased cardiac risk; therefore, non-anthracycline chemotherapy may be appropriate for patients with cardiovascular risk factors.…”

Section: Discussionmentioning

confidence: 99%

Long-term outcomes of neoadjuvant trastuzumab emtansine + pertuzumab (T-DM1 + P) and docetaxel + carboplatin + trastuzumab + pertuzumab (TCbHP) for HER2-positive primary breast cancer: results of the randomized phase 2 JBCRG20 study (Neo-peaks)

Takano,

Masuda,

Ito

et al. 2024

Breast Cancer Res Treat

View full text Add to dashboard Cite

Purpose The randomized phase 2 Neo-peaks study examined usefulness of neoadjuvant trastuzumab emtansine + pertuzumab (T-DM1 + P) following docetaxel + carboplatin + trastuzumab + pertuzumab (TCbHP) as compared with the standard TCbHP regimen. We previously reported that pCR rate after neoadjuvant therapy tended to be higher with TCbHP followed by T-DM1 + P. We conducted an exploratory analysis of prognosis 5 years after surgery. Methods Neoadjuvant treatment with TCbHP (6 cycles; group A), TCbHP (4 cycles) followed by T-DM1 + P (4 cycles; group B), and T-DM1 + P (4 cycles; group C, + 2 cycles in responders) were compared. Group C non-responders after 4 cycles were switched to an anthracycline-based regimen. We evaluated 5-year disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS). Results Data from 203 patients (50, 52, and 101 in groups A–C, respectively) were analyzed. No significant intergroup differences were found for DFS, DDFS, or OS. The 5-year DFS rates (95% CI) were 91.8% (79.6–96.8%), 92.3% (80.8–97.0%), and 88.0% (79.9–93.0%) in groups A–C, respectively. TCbHP followed by T-DM1 + P and T-DM1 + P with response-guided addition of anthracycline therapy resulted in similar long-term prognosis to that of TCbHP. Conclusions In patients who achieved pCR after neoadjuvant therapy with T-DM1 + P, omission of adjuvant anthracycline may be considered, whereas treatment should be adjusted for non-pCR patients with residual disease. T-DM1 + P with response-guided treatment adjustment may be useful for minimizing toxicity. Trial registration number and date of registration UMIN-CTR, UMIN000014649, prospectively registered July 25, 2014. Some of the study results were presented as a Mini Oral session at the ESMO Breast Cancer 2023 (Berlin, Germany, 11–13 May 2023).

show abstract

Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial

Cited by 10 publications

References 27 publications

GDF-15 is a potential candidate biomarker for an elevated risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy

GDF-15 is a potential candidate biomarker for an elevated risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy

Circulating microRNAs and therapy-associated cardiac events in HER2-positive breast cancer patients: an exploratory analysis from NeoALTTO

Long-term outcomes of neoadjuvant trastuzumab emtansine + pertuzumab (T-DM1 + P) and docetaxel + carboplatin + trastuzumab + pertuzumab (TCbHP) for HER2-positive primary breast cancer: results of the randomized phase 2 JBCRG20 study (Neo-peaks)

Contact Info

Product

Resources

About