Perjeta (pertuzumab)

Fifteen studies that met the established inclusion criteria were analyzed, and their methodological quality was assessed using the Joanna Briggs Institute approach, demonstrating high reliability in the results obtained, the analyzed studies focus on the combination of adjuvant Pertuzumab + Trastuzumab with chemotherapy for the treatment of HER2-positive breast cancer. Scientific evidence suggests that the combination of pertuzumab and trastuzumab not only improves the survival of patients with HER2-positive breast cancer but also provides a safe and flexible treatment option.

P1/2, N=81, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

Collectively, anti-HER2 IgE maintains Fab-mediated antitumor activity, induces Fc-mediated effects against HER2-expressing tumor cells, and stimulates remodeling of the immune microenvironment in tumors to promote pro-inflammatory cell phenotypes which could translate to improved outcomes for patients.

Before neoadjuvant chemotherapy combined with H and P dual-target therapy, ALT levels were associated with pCR. After the treatment, GGT levels were linked to pCR. This treatment regimen was associated with increased blood levels of ALT, AST, LDH, and GGT.

P2, N=48, Recruiting, Carey Anders, M.D. | Trial completion date: Oct 2027 --> Jul 2026 | Trial primary completion date: Oct 2026 --> Apr 2026

P2, N=39, Active, not recruiting, The Methodist Hospital Research Institute | Recruiting --> Active, not recruiting | Trial completion date: Feb 2025 --> Dec 2025

Such dynamic fluctuation of receptor interaction may open a window for the binding of therapeutic antibodies that are aimed at inhibiting heterodimerization, such as pertuzumab. The complementary array of state-of-the-art imaging cytometry approaches thus demonstrates a spatiotemporal pattern of spontaneous and induced receptor aggregation states that could provide mechanistic insights into the potential success of targeted therapies directed at the HER family of receptor tyrosine kinases.

This is the first study to report the efficacy and safety of third-generation HER2-directed ADC in the neoadjuvant setting for HER2-positive breast cancer. SHR-A1811 showed robust activity, with a tolerable safety profile. (ClinicalTrials.gov, NCT05582499).

The HER2/PET-CT biomarker had high prediction power for pCR, however was not superior to the prediction power of PET/CT alone. Non-invasive PET/CT biomarkers may facilitate a response-guided approach to neoadjuvant therapy, allowing intensification and de-intensification of treatment, pending further evaluation.

P2, N=7, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2027

The phase 2 NA-PHER2 trial (NCT02530424) investigated chemo-free preoperative HER2 blockade (trastuzumab + pertuzumab) and CDK4/6 inhibition (palbociclib) with or without endocrine therapy (fulvestrant) in HER2+ER+ breast cancer. The LowLow group exhibited a Luminal A phenotype by the end of treatment. This study expands our understanding of drivers and dynamics of HER2+ER+ tumour response, towards treatment tailoring.

These data provide a robust preclinical characterization of XMT-2056 and provide rationale and strategy for its clinical testing.

P1, N=37, Completed, Bavarian Nordic | N=55 --> 37 | Active, not recruiting --> Completed

P2, N=63, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> May 2025

P2, N=53, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2025 --> Oct 2026 | Trial primary completion date: Jan 2025 --> Oct 2025

P2, N=171, Completed, European Organisation for Research and Treatment of Cancer - EORTC | Active, not recruiting --> Completed | Trial completion date: Dec 2028 --> Dec 2024

P2, N=23, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Nov 2024 --> Nov 2025

P2, N=220, Completed, West German Study Group | Active, not recruiting --> Completed

P3, N=900, Active, not recruiting, Shanghai Henlius Biotech | Trial primary completion date: Nov 2024 --> May 2024

Additionally, we identified key proteins, including ANXA1, SLC2A1, and PPIG, which contribute to the tumour progression and resistance phenotype. Our study suggests that targeting these pathways and proteins could form the basis of novel therapeutic strategies to overcome resistance in HER2-positive breast cancer.

Pyrotinib combined with trastuzumab may offer an effective neoadjuvant treatment option for HER2-positive breast cancer, with a superior efficacy over trastuzumab alone. However, pyrotinib plus trastuzumab did not show better efficacy compared with Per + H. Pyrotinib plus trastuzumab was associated with more diarrhrea than trastuzumab monotherapy. In addition, P + H is less cost-effective compared with the combination of Per + H.

P2, N=8, Recruiting, Mayo Clinic | N=25 --> 8

P2, N=170, Recruiting, UNICANCER | Not yet recruiting --> Recruiting

P3, N=347, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Mar 2025 --> Nov 2024

P1/2, N=245, Active, not recruiting, AstraZeneca | Trial completion date: Jan 2025 --> Jan 2030

Pertuzumab and pyrrolizinib target HER-2 to downregulate the PI3K/AKT signaling pathway, thereby inhibiting breast cancer cells.

Chemotherapy was initiated with a regimen of paclitaxel, trastuzumab, and pertuzumab...However, after 9 months of treatment, disease progression occurred, leading to sequential changes in the treatment regimen to T-DM1 and T-DXd...Postoperatively, the patient received radiation therapy to the chest wall, followed by continued treatment with trastuzumab and pertuzumab. As of 2 years after surgery, no recurrence has been observed.

Without distant metastasis, the patient received doxorubicin plus cyclophosphamide( AC)therapy followed by trastuzumab, pertuzumab, docetaxel(HPD)therapy as neoadjuvant chemotherapy. Subseqently, the tumor disappeared clinically. Mastectomy was performed, and complete response was confirmed pathologically.

P2, N=2, Active, not recruiting, Spanish Breast Cancer Research Group | Recruiting --> Active, not recruiting | N=41 --> 2

P2, N=11, Terminated, Bolt Biotherapeutics, Inc. | Trial completion date: Mar 2025 --> Sep 2024 | Active, not recruiting --> Terminated; Sponsor Decision

P=N/A, N=2907, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2025 --> Jun 2026 | Trial primary completion date: Nov 2025 --> Jun 2026

Although this regimen exhibits high rates of response and disease control in both HR+ and HR- cohorts, some patients could have intrinsic or develop acquired resistance to trastuzumab and/or pertuzumab. Here, we achieved a near-complete response in HR+ HER2-amplified and overexpressing metastatic BC twice through molecular tumor board (MTB) initially, with trastuzumab deruxtecan (T-DXd) when HER2 IHC was positive, and, then, with neratinib plus fulvestrant plus paclitaxel when IHC was negative...Furthermore, we demonstrated that triplet combination could induce a remarkable response in the T-DXd-refractory setting, which could be explored in future clinical trials in HR+ and HER2-activated (by RNA or protein overexpression, amplification, and mutation) patients. Our case also highlights the importance of the MTBs to dynamically and reactively manage the course of disease and treatment on a per-patient basis.

P2, N=63, Recruiting, Latin American Cooperative Oncology Group | Not yet recruiting --> Recruiting

P2, N=74, Not yet recruiting, University of Chicago | Initiation date: Jan 2025 --> Jan 2026

P2, N=528, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Nov 2024

The standard of care for HER2-positive and hormone receptor-positive breast cancer patients who receive neoadjuvant chemotherapy (NACT) combined with trastuzumab, with or without pertuzumab, is to continue with adjuvant T-DM1 in cases of an incomplete response according to KATHERINE trial results. However, the optimal management for patients with residual disease with loss of HER2 expression is not widely studied. Loss of HER2 expression after NACT with anti HER2 is a rarer event with questionable value both as a predictive prognostic marker.

Subsequently, she underwent post-operative chemotherapy regimen of doxorubicin, cyclophosphamide, T-docetaxel and trastuzumab (AC-TH) and then received maintenance treatment with trastuzumab and pertuzumab. If possible, dual anti-HER2 therapy combined with trastuzumab and pertuzumab is recommended. Finally, positive clinical prognosis of PBSCC may be attributed to early detection, immediate surgery, precise diagnosis and proper adjuvant treatment strategy.

PCR rates were similar overall between ACTHP and DCbHP; however, in the HER2 3+ subgroup, ACTHP demonstrated increased efficacy. DCbHP was significantly less cardiotoxic.

Median PFS by independent review did not show the difference between the two groups (4.4 v 4.4 months; HR, 1.03 [one side 95% CI upper limit, 1.36]). These findings suggest that dual HER2 blockade with pertuzumab plus trastuzumab could contribute to improving OS in patients who have previously been treated with pertuzumab-containing regimens for HER2-positive LA/mBC.

P2, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jun 2025

The HER2DX pCR score could predict pCR in stage III HER2-positive IBC following treatment with de-escalated neoadjuvant systemic therapy and in stage III HER2-positive non-IBC. Elevated pCR rates in HER2-positive IBC with high HER2DX pCR scores suggest there may be a role for treatment de-escalation in these patients and confirmatory studies are justified.

P=N/A, N=120, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine