De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR− phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel

Nitz, Ulrike; Gluz, Oleg; Christgen, Matthias; Grischke, EM; Augustin, Doris; Küemmel, Sherko; Braun, Michael; Potenberg, Jochem; Kohls, A.; Krauss, Katja; Stefek, Andrea; Schumacher, Claudia; Forstbauer, Helmut; Reimer, Toralf; Fischer, Hans Holger; Liedtke, Cornelia; Wuerstlein, Rachel; Schumacher, Johannes; Kates, Ronald; Kreipe, Hans; Harbeck, Nadia

doi:10.1093/annonc/mdx494

Cited by 123 publications

(117 citation statements)

References 29 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…The addition of pertuzumab to a taxane and trastuzumab as first‐line treatment in advanced, HER2‐positive breast cancer improved OS by almost 16 months . The activity of pertuzumab also has been studied in the neoadjuvant setting in several phase 2 trials (Table ) . The NeoSphere trial demonstrated that dual‐blockade with pertuzumab and trastuzumab plus chemotherapy produced a significantly improved pCR rate in the breast compared with chemotherapy and trastuzumab alone (46% vs 29%, respectively).…”

Section: Trastuzumab a Landmark In The Treatment Of Her2‐positive DImentioning

confidence: 99%

“…Recently, the West‐German Study Group ADAPT trial evaluated the efficacy of 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab with or without weekly paclitaxel in the HER2‐positive/HR‐negative subgroup. That study, with a focus on early responders, demonstrated an impressive pCR rate of 90.5% in the dual blockade plus paclitaxel arm . This pCR rate is the highest ever reported and compares favorably with the rates reported is studies with longer and more aggressive chemotherapy regimens.…”

Section: Trastuzumab a Landmark In The Treatment Of Her2‐positive DImentioning

confidence: 99%

“…To date, dual blockade with trastuzumab and pertuzumab plus chemotherapy should be considered the standard of care for patients with HER2‐positive breast cancer who meet criteria for neoadjuvant treatment. In patients who have tumors measuring <2 cm and no lymph node involvement (ie, clinical T1N0 disease), there are no data to recommend neoadjuvant treatment with pertuzumab . Moreover, considering the excellent outcomes of patients with small HER2‐positive breast cancers who received adjuvant paclitaxel and trastuzumab (the APT trial), as described below, in most of these patients, adjuvant treatment should be recommended (see Fig.…”

Section: Trastuzumab a Landmark In The Treatment Of Her2‐positive DImentioning

confidence: 99%

“…Another approach to de‐escalating therapy in select patients may be to use less intense chemotherapy regimens with optimized anti‐HER2 therapy or to substitute chemotherapy with effective targeted therapies. The highest pCR rates in HER2‐positive disease have been reported with chemotherapy plus dual anti‐HER2 therapy, especially in the subset of patients with HER2‐positive/HR‐negative tumors . However, highly effective biologic therapy can eradicate HER2‐positive tumors in a proportion of patients with a favorable toxicity profile, and chemotherapy may represent an overtreatment in these patients.…”

Section: Novel Approaches To Her2‐positive Early Breast Cancermentioning

confidence: 99%

“…However, highly effective biologic therapy can eradicate HER2‐positive tumors in a proportion of patients with a favorable toxicity profile, and chemotherapy may represent an overtreatment in these patients. Dual‐HER2 blockade alone with or without endocrine therapy has produced activity in terms of pCRs in a substantial percentage of patients . Similarly, the neoadjuvant, phase 2, open‐label NA‐PHER trial explored the combination of trastuzumab, pertuzumab, palbociclib, and fulvestrant in patients with HER2‐positive, estrogen receptor (ER)‐positive breast cancer.…”

Section: Novel Approaches To Her2‐positive Early Breast Cancermentioning

confidence: 99%

See 4 more Smart Citations

Optimal treatment of early stage HER2‐positive breast cancer

Pernas

Barroso‐Sousa

Tolaney

2018

Cancer

View full text Add to dashboard Cite

Significant advances have occurred in the treatment of human epidermal growth factor receptor 2 (HER2)‐positive breast cancer that have changed its natural history. The addition of trastuzumab to standard therapy has dramatically improved the prognosis for patients with early stage, HER2‐positive breast cancer to unprecedented survival outcomes. Yet, long‐term follow‐up data from adjuvant pivotal trials indicate that 15‐24% of patients still develop recurrent disease. Most of the research has focused on the addition of novel anti‐HER2 drugs to standard therapy, including studies evaluating the monoclonal antibody pertuzumab; the antibody‐drug conjugate trastuzumab‐emtansine (T‐DM1); the selective, reversible HER2/epidermal growth factor receptor kinase inhibitor lapatinib; or the irreversible pan‐HER2 inhibitor neratinib. Dual HER2 blockade has improved overall survival remarkably in metastatic breast cancer; however, in patients with early stage disease, it has led to small benefits in progression‐free survival. Moreover, biologic heterogeneity within HER2‐positive disease may determine response to treatment and prognosis. Different subgroups of patients with HER2‐positive breast cancer may benefit from different therapeutic approaches. Thus, there is ongoing work to optimize and de‐escalate treatment in patients who may do just as well with less therapy and can avoid unnecessary treatments and their related toxicities. The objective of this review is to summarize the background and latest evidence on the current management of early stage, HER2‐positive breast cancer and to present novel perspectives on its management.

show abstract

Section: Trastuzumab a Landmark In The Treatment Of Her2‐positive DImentioning

confidence: 99%

Section: Trastuzumab a Landmark In The Treatment Of Her2‐positive DImentioning

confidence: 99%

Section: Trastuzumab a Landmark In The Treatment Of Her2‐positive DImentioning

confidence: 99%

Section: Novel Approaches To Her2‐positive Early Breast Cancermentioning

confidence: 99%

Section: Novel Approaches To Her2‐positive Early Breast Cancermentioning

confidence: 99%

See 3 more Smart Citations

Optimal treatment of early stage HER2‐positive breast cancer

Pernas

Barroso‐Sousa

Tolaney

2018

Cancer

View full text Add to dashboard Cite

show abstract

Efficacy of Endocrine Therapy Plus Trastuzumab and Pertuzumab vs De-escalated Chemotherapy in Patients with Hormone Receptor–Positive/ERBB2-Positive Early Breast Cancer

et al. 2023

View full text Add to dashboard Cite

ImportanceCombination of chemotherapy with (dual) ERBB2 blockade is considered standard in hormone receptor (HR)-positive/ERBB2-positive early breast cancer (EBC). Despite some promising data on endocrine therapy (ET) combination with dual ERBB2 blockade in HR-positive/ERBB2-positive BC, to our knowledge, no prospective comparison of neoadjuvant chemotherapy vs ET plus ERBB2 blockade in particular with focus on molecular markers has yet been performed.ObjectiveTo determine whether neoadjuvant de-escalated chemotherapy is superior to endocrine therapy, both in combination with pertuzumab and trastuzumab, in a highly heterogeneous HR-positive/ERBB2-positive EBC.Design, Setting, and ParticipantsThis prospective, multicenter, neoadjuvant randomized clinical trial allocated 207 patients with centrally confirmed estrogen receptor–positive and/or progesterone receptor–positive (&gt;1%) HR-positive/ERBB2-positive EBC to 12 weeks of standard ET (n = 100) vs paclitaxel (n = 107) plus trastuzumab and pertuzumab. A total of 186 patients were required to detect a statistically significant difference in pathological complete response (pCR) (assumptions: 19% absolute difference in pCR; power, ≥80%; 1-sided Fisher exact test, 2.5% significance level).InterventionsStandard ET (aromatase inhibitor or tamoxifen) or paclitaxel, 80 mg/m2, weekly plus trastuzumab and pertuzumab every 21 days.Main Outcomes and MeasuresThe primary end point was pCR (ypT0/is, ypN0). Secondary end points included safety, translational research, and health-related quality of life. Omission of further chemotherapy was allowed in patients with pCR. PAM50 analysis was performed on baseline tumor biopsies.ResultsOf the 207 patients included (median [range] age, 53 [25-83] years), 121 (58%) had cT2 to cT4 tumors, and 58 (28%) had clinically node-positive EBC. The pCR rate in the ET plus trastuzumab and pertuzumab arm was 23.7% (95% CI, 15.7%-33.4%) vs 56.4% (95% CI, 46.2%-66.3%) in the paclitaxel plus trastuzumab and pertuzumab arm (odds ratio, 0.24; 95% CI, 0.12-0.46; P &lt; .001). Both immunohistochemical ERBB2 score of 3 or higher and ERBB2-enriched subtype were independent predictors for pCR in both arms. Paclitaxel was superior to ET only in the first through third quartiles but not in the highest ERBB2 quartile by messenger RNA. In contrast with the paclitaxel plus trastuzumab and pertuzumab arm, no decrease in health-related quality of life after 12 weeks was observed in the ET plus trastuzumab and pertuzumab arm.Conclusions and RelevanceThe WSG-TP-II randomized clinical trial is, to our knowledge, the first prospective trial comparing 2 neoadjuvant de-escalation treatments in HR-positive/ERBB2-positive EBC and demonstrated an excellent pCR rate after 12 weeks of paclitaxel plus trastuzumab and pertuzumab that was clearly superior to the pCR rate after ET plus trastuzumab and pertuzumab.Trial RegistrationClinicalTrials.gov Identifier: NCT03272477

show abstract

Breast Cancer

2022

Fundamentals of Cancer Detection, Treatment, and Prevention

View full text Add to dashboard Cite

De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR− phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel

Cited by 123 publications

References 29 publications

Optimal treatment of early stage HER2‐positive breast cancer

Optimal treatment of early stage HER2‐positive breast cancer

Efficacy of Endocrine Therapy Plus Trastuzumab and Pertuzumab vs De-escalated Chemotherapy in Patients with Hormone Receptor–Positive/ERBB2-Positive Early Breast Cancer

Breast Cancer

Contact Info

Product

Resources

About