Perjeta (pertuzumab)

Our study revealed novel functions of DLL4 in cell stemness and immune infiltration, including NET formation and T cell exclusion, which collectively contributed to THP neoadjuvant therapy resistance in HER2+ BC. Furthermore, we provided a CAR-T-based therapy to sensitize the THP neoadjuvant therapy.

The economic viability of dual HER2-targeted therapy was most pronounced in patients with node-positive high-risk early breast cancer. This study highlights the potential of dual HER2-targeted therapy as a cost-effective addition for these cases.

P2, N=220, Active, not recruiting, West German Study Group | Recruiting --> Active, not recruiting | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Aug 2015 --> Jan 2025

P1/2, N=81, Not yet recruiting, Merck Sharp & Dohme LLC

P2, N=402, Recruiting, West German Study Group | Not yet recruiting --> Recruiting

P3, N=700, Recruiting, IFOM ETS - The AIRC Institute of Molecular Oncology | Not yet recruiting --> Recruiting

P2, N=86, Completed, UNICANCER | Active, not recruiting --> Completed

Multiple logistic regression analysis showed that pertuzumab (PER) use, high alkaline phosphatase (ALP), and low high-density lipoprotein (HDL) cholesterol levels were associated with IR. IR should be considered when PER is combined with TRA. ALP and HDL cholesterol levels may be predictive markers of TRA-induced IR in patients with breast cancer.

No abstract available

Consequently, we determined that the patient presented with a condition similar to immune thrombocytopenic purpura (ITP) and selected a treatment approach consisting of eltrombopag, a thrombopoietin receptor agonist. Although uncommon, anti-HER2 antibodies can cause severe thrombocytopenia. Furthermore, if thrombocytopenia persists after treatment discontinuation and the administration of corticosteroids, exploring treatment options aligned with managing ITP is essential.

In those with RD, 36% lost HER2(+) status; IDFS events appeared similar in those with HER2(+) RD versus those with HER2(-) RD. The BM events seen in those with RD and pCR highlights the need for more effective therapy in NAST and adjuvant setting to minimize BM risk.

P=N/A, N=50, Enrolling by invitation, Nagoya City University

Dual human epidermal growth factor receptor 2(HER2)blockade with trastuzumab(H)and pertuzumab(P)combined with docetaxel and carboplatin(TCb)is a standard neoadjuvant therapy for HER2-positive breast cancer patients. 4 cycles of T-DM1+P). Simultaneous administration of H and P enables a reduced administration time, which would benefit both patients and healthcare providers.

Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved an adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling.

Undifferentiated thyroid cancer (ATC) is highly malignant and does not respond well to sorafenib (SRF) treatment owing to the lack of specificity of SRF targeting...Therefore, we developed a pH-responsive nano-targeted drug delivery systems using human serum albumin (HSA) as a carrier to generate manganese dioxide (MnO2)@HSA nanoparticles (NPs), then encapsulated SRF and the fluorescent dye indocyanine green (ICG) and finally modifyed the targeting antibody pertuzumab in the outer layer of the nano complexes, resulting in SRF/ICG/MnO2@HSA-pertuzumab (HISMP) NPs...In vivo MR/NIRF imaging experiments confirmed that the HISMP NPs specifically aggregated at tumor sites and have good in vivo MR/NIRF imaging ability and effective anti-tumor activity. The nano-delivery system is expected to provide a theoretical foundation for the efficient ATC diagnosis and therapy.

The patient received neoadjuvant chemotherapy with epirubicin and cyclophosphamide, followed by docetaxel, trastuzumab, and pertuzumab...A liver biopsy following treatment with trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-Dxd) revealed HER2-negative status. Cyclin-dependent kinase (CDK) 4/6 inhibitor combination endocrine therapy has been continued for 16 months to date while maintaining tumor shrinkage. It is essential to perform a rebiopsy during treatment to optimize therapy based on the subtype.

Finally, phase II clinical trials involving HER2-altered NSCLC patients demonstrated promising treatment outcomes with trastuzumab deruxtecan, trastuzumab emtansine, pyrotinib, pyrotinib + apatinib and trastuzumab + pertuzumab + docetaxel. In conclusion, the prevalence of HER2 alteration among Malaysian NSCLC patients falls within the global range. A systematic review of clinical trials revealed promising treatment outcomes and Malaysian NSCLC patients with HER2 alterations are anticipated to similarly benefit from HER2-targeted therapies.

P2, N=53, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting

By analyzing two large and diverse datasets from multiple perspectives, we obtained reliable results that the trastuzumab originator and its biosimilars have similar safety profiles. The concurrent use of pertuzumab was also found to be safe. The use of biosimilars can lead to cost savings. These findings provide crucial insights for the evaluation and adoption of biosimilars in clinical practice.

P3, N=180, Not yet recruiting, Prof. Wolfgang Janni

P4, N=200, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Our results are in line with the CLEOPATRA and EMILIA studies, but long-term responders in the arm A may have impacted our results. The absence of difference in term of PFS in first metastatic line may be explained by a selection bias, as patients in the arm A potentially have more aggressive forms.

HER2-targeted drugs such as HerceptinTM (trastuzumab), PERJETA® (pertuzumab) and KADCYLA® (adotrastuzumab emtansine) are beneficial for HER2-positive breast cancer patients who will inhibit cell signaling pathways. If the FISH results are negative for HER2 IHC equivocal, this is considered HER2-Low. Significantly, Enhertu has shown a promising objective response in HER2-Low breast cancer patients.

P2, N=20, Suspended, University of Rochester | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Jun 2026

P1, N=68, Completed, Otto Metzger, MD | Active, not recruiting --> Completed

P3, N=516, Active, not recruiting, Helsinki University Central Hospital | Trial primary completion date: Dec 2021 --> Jul 2025

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

Targeted therapies like trastuzumab deruxtecan (T-DXd), trastuzumab, pertuzumab, and T-DM1 have revolutionized HER2-positive metastatic breast cancer (MBC) treatment. Personalized approaches have boosted HER2-positive MBC outcomes, and ongoing research is crucial to uncover new treatments and biomarkers, potentially elevating long-term response rates and prognoses. This may aid in providing new direction to breast cancer clinics.

Managing Li-Fraumeni syndrome (LFS) and its associated cancers, particularly in young patients, necessitates a comprehensive and multidisciplinary approach. Early genetic testing for TP53 mutations is crucial in identifying LFS, enabling personalized treatment plans and proactive surveillance strategies.

Drug-induced lupus is a clinical syndrome that shares similar features with systemic lupus erythematosus (SLE). The majority of patients present with symptoms such as arthralgia and myalgia. Hydralazine and procainamide are high-risk drugs for drug-induced lupus. Symptoms usually develop after months or years of use, but may also develop suddenly. Our patient also received TDM-1 treatment for 18 months. We present a case of TDM-1-associated drug-induced lupus in a patient with metastatic breast cancer. This is the first case of TDM-1-related drug-induced lupus reported in the literature.

P3, N=19, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

In November 2013, for neck nodal progression, seven cycles of chemotherapy (cisplatin and epirubicin) associated with a humanized monoclonal antibody-targeting HER 2 therapy (trastuzumab and pertuzumab) were performed, with a marked response rate. In primary ductal adenocarcinoma of the lacrimal gland, early diagnosis and multimodal treatments could be crucial, considering its often aggressive tendency. Considering the lack of treatment guidelines, case report recording can be useful in patient management.

The TCbHP regimen (docetaxel, carboplatin, trastuzumab, and pertuzumab) as neoadjuvant chemotherapy was given. Our clinical experience suggests that neoadjuvant chemotherapy followed by modified radical mastectomy can be effective for treating such rare cases. The patient achieved pCR, which can provide a therapeutic strategy for effective treatment of similar OBCs.

P1/2, N=39, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2024 --> Jul 2025 | Trial primary completion date: Nov 2024 --> Jul 2025

P4, N=250, Not yet recruiting, Danish Breast Cancer Cooperative Group

P2, N=3791, Recruiting, American Society of Clinical Oncology | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Jun 2026

P3, N=654, Active, not recruiting, Seagen Inc. | Trial completion date: Jun 2027 --> Oct 2027 | Trial primary completion date: Oct 2024 --> May 2025

HER2-targeted therapy plus chemotherapy demonstrated high efficacy in most patients, reducing the statistical power for finding immunological markers. However, NK subset phenotypes correlated better with response groups, and numerous changes in the percentage of leukocytes and T and NK cells, as well as changes in the functionality of NK cells, were observed in most patients after treatment, encouraging further research into these immune populations.

The iDFS benefit was seen in the hormone receptor-negative (HR, 0.82 [95% CI, 0.64 to 1.06]) and HR+ cohorts (HR of 0.75 [95% CI, 0.61 to 0.92]). Despite improvement in overall iDFS, the addition of pertuzumab did not improve OS at this third interim analysis.

P3 | N=808 | CLEOPATRA (NCT00567190) | Sponsor: Genentech, Inc. | "REVEAL GENOMICS S.L...released further evidence supporting HER2DX, the world’s first specialized genomic test for HER2+ breast cancer. These results were obtained in collaboration with F. Hoffmann-La Roche Ltd (Basel, Switzerland) after analyzing HER2DX in tumor samples from the CLEOPATRA phase III clinical trial (NCT00567190)....For the first time, the investigators evaluated the ability of the HER2DX ERBB2 mRNA score to predict long-term survival outcomes in 214 patients treated with THP in the pivotal CLEOPATRA phase III trial3. The results showed a strong association of HER2DX ERBB2 mRNA score with PFS and OS....Detailed results of this study will be presented at an upcoming medical congress and submitted for publication."

The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive breast cancer brain metastases.

After the standard first-line treatment including albumin-bound paclitaxel, trastuzumab and pertuzumab, and a second-line treatment involving pyrotinib, capecitabine, and radiotherapy did not produce the desired results, the patient was then administered anlotinib in combination with pyrotinib and letrozole as a third-line treatment, which led to a partial response (PR). The findings suggest that anti-angiogenic therapy, specifically anlotinib, could be regarded as a promising therapeutic option for BC patients with BM.