Patient-reported function, health-related quality of life, and symptoms in APHINITY: pertuzumab plus trastuzumab and chemotherapy in HER2-positive early breast cancer

Bines, José; Clark, Emma; Barton, Claire; Restuccia, Eleonora; Procter, Marion; Sonnenblick, Amir; Fumagalli, Debora; Parlier, Damien; Arahmani, Amal; Baselga, José; Viale, Giuseppe; Reaby, Linda; Frank, Elizabeth S.; Gelber, Richard D.; Piccart, Martine; Jackisch, Christian; Petersen, Jennifer

doi:10.1038/s41416-021-01323-y

Cited by 5 publications

(12 citation statements)

References 16 publications

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“…Furthermore, disease recurrence in the pertuzumab group was reduced. Much like the phase II studies, the addition of pertuzumab to a trastuzumab and chemotherapy treatment regimen did not result in any significant increase in adverse effects other than elevated diarrhea scores [70].…”

Section: Pertuzumab (2c4)mentioning

confidence: 71%

“…Here, the addition of pertuzumab significantly increased PFS by several months without any increase in cardiac toxicity (Table 1). In the APHINITY clinical trials [52,70], patients with early HER2-positive breast cancer were treated with pertuzumab or placebo in combination with trastuzumab and chemotherapy. HER2-positive breast cancer patients treated with pertuzumab showed significant improvement in the 3-year invasive disease-free survival rate compared to the placebo group.…”

Section: Pertuzumab (2c4)mentioning

confidence: 99%

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Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

Holloway

Marignani

2021

Cancers

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Up to one third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mechanistic target of rapamycin (mTOR) pathway activity and a metabolic shift to glycolysis. Although inhibitors targeting the HER2 receptor have been successful in treating HER2-positive breast cancer, anti-HER2 therapy is associated with a high risk of recurrence and drug resistance due to stimulation of the PI3K-Akt-mTOR signaling pathway and glycolysis. Combination therapies against HER2 with inhibition of mTOR improve clinical outcomes compared to HER2 inhibition alone. Here, we review the role of the HER2 receptor, mTOR pathway, and glycolysis in HER2-positive breast cancer, along with signaling mechanisms and the efficacy of treatment strategies of HER2-positive breast cancer.

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Section: Pertuzumab (2c4)mentioning

confidence: 71%

Section: Pertuzumab (2c4)mentioning

confidence: 99%

Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

Holloway

Marignani

2021

Cancers

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“…However, this increase appeared to be associated with chemotherapy since rates were similar in the post-chemotherapy treatment period (grade ≥ 3 diarrhea 0.5% with pertuzumab plus trastuzumab and 0.2% with placebo plus trastuzumab) [ 22 ]. Notably, patient-reported outcome data indicated similar levels of role, social, cognitive, and emotional functioning in both treatment groups, suggesting that patients were able to maintain their functioning even in the context of increased diarrhea [ 27 ]. There was also a modest increase in the incidence of New York Heart Association (NYHA) class III or IV heart failure with an LVEF decline to <50% and by ≥10 percentage points from baseline (0.6% with pertuzumab plus trastuzumab and 0.2% with placebo plus trastuzumab) [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Event-Free Survival in Patients with Early HER2-Positive Breast Cancer with a Pathological Complete Response after HER2-Targeted Therapy: A Pooled Analysis

Swain

Macharia

Cortés

et al. 2022

Cancers

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The standard-of-care for patients with pathological complete response (pCR) after neoadjuvant human epidermal growth factor receptor 2 (HER2)-targeted therapy plus chemotherapy is continuation of HER2-targeted therapy in the adjuvant setting. Our objective was to evaluate risk of recurrence or death in these patients and determine if outcomes differed by the HER2-targeted regimen received in each setting. We analyzed patient-level data from five randomized trials evaluating trastuzumab, pertuzumab, or both as part of systemic neoadjuvant and adjuvant therapy for HER2-positive early breast cancer, and assessed event-free survival (EFS) in 1763 patients. Patients with pCR had decreased risk of an EFS event versus those with residual disease (unadjusted hazard ratio [HR] = 0.35; 95% confidence interval [CI]: 0.27–0.46). Regardless of pCR status, after adjusting for baseline factors, reduction in EFS event risk was greater in patients administered pertuzumab/trastuzumab in both settings versus those administered only trastuzumab in both settings (HR = 0.36; 95% CI: 0.26–0.49), or pertuzumab/trastuzumab in the neoadjuvant setting and only trastuzumab in the adjuvant setting (HR = 0.67; 95% CI: 0.47–0.96). Patients with pCR had longer EFS than those with residual disease. Patients treated with pertuzumab/trastuzumab in both the neoadjuvant and adjuvant settings had the lowest risk of breast cancer recurrence.

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“…Eighty-one articles were eliminated according to stricter application of the inclusion criteria, leaving ten studies for our present analysis, with four of these studies being eligible for metaanalysis (Au et al, 2013;Syrios et al, 2018;Trinca et al, 2019;Conte et al, 2020). Six articles were excluded from quantitative meta-analysis due to lack of detailed data for allowing metaanalysis (Earl et al, 2020;Sawaki et al, 2020Sawaki et al, , 2022Sella et al, 2022) or comparing trastuzumab in both arms (Bines et al, 2021;Taira et al, 2021). The details of the selection process are described in Figure 1.…”

Section: Selection Criteriamentioning

confidence: 99%

“…The included studies consisted of seven RCTs (Au et al, 2013;Conte et al, 2020;Earl et al, 2020;Sawaki et al, 2020;Bines et al, 2021;Taira et al, 2021;Sella et al, 2022) and three observational studies of cross-sectional design (Syrios et al, 2018;Trinca et al, 2019;Sawaki et al, 2022). Two studies (Trinca et al, 2019;Conte et al, 2020) involved the comparison of a group receiving trastuzumab treatment with a group receiving chemotherapy.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Health-related quality of life in Her2-positive early breast cancer woman using trastuzumab: A systematic review and meta-analysis

et al. 2023

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Background: Despite the benefits of trastuzumab in many trials, evidence of its impact on health-related quality of life (HRQoL) in early treatment has not been summarized. This study explored the effects of trastuzumab treatment on HRQoL, including pooled meta-analysis, in an effort to provide an integrated assessment of HRQoL for Her2-positive early breast cancer patients.Methods: A comprehensive literature review to February 2023 using three databases, focusing on treatment using trastuzumab during the early stage, was performed. The mean changes from baseline during and after treatment were extracted from the included randomized control trials (RCTs) papers and total HRQoL scores were obtained from cross-sectional studies included. Mean difference (MD) and 95% confidence intervals were assessed by a random effect or fixed effect model based on heterogeneity (I2).Results: A total of ten studies were identified and reviewed, consisting of seven RCTs and three cross-sectional studies. The pooled analysis of the mean change from baseline during treatment resulted in an MD of 1.92 (95% CI = 1.59 to 2.25, p < 0.05, I2 = 0%), favoring the trastuzumab group. A non-significant result of the mean change from baseline after treatment appeared in the analysis of 12-month follow-up. In the cross-sectional studies, pooled analyses of HRQoL showed that trastuzumab meaningfully demonstrated an improved HRQoL profile (MD = 9.29, 95% CI = 1.31 to 17.27, p = 0.02, I2 = 0%).Conclusion: Trastuzumab as a targeted therapy resulted in a favorable effect on HRQoL in the early stages of Her2-positive breast cancer. The findings of significant improvements in patients’ HRQoL and less clinically meaningful deterioration in side effects of trastuzumab-containing regimen during treatment were supported by prolonged survival.

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Patient-reported function, health-related quality of life, and symptoms in APHINITY: pertuzumab plus trastuzumab and chemotherapy in HER2-positive early breast cancer

Cited by 5 publications

References 16 publications

Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

Event-Free Survival in Patients with Early HER2-Positive Breast Cancer with a Pathological Complete Response after HER2-Targeted Therapy: A Pooled Analysis

Health-related quality of life in Her2-positive early breast cancer woman using trastuzumab: A systematic review and meta-analysis

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