Perjeta (pertuzumab)

P2, N=175, Active, not recruiting, German Cancer Research Center | Recruiting --> Active, not recruiting

The patient was diagnosed as having stage IV HER2-positive breast cancer, which was treated with a regimen of trastuzumab (8 mg/kg), pertuzumab (first dose: 840 mg; second dose onward: 420 mg) and docetaxel (75 mg/m2) every 3 weeks. After 4 months of chemotherapy, the patient received complete remission. In conclusion, concomitant use of rifampicin and clarithromycin may increase the blood concentration of docetaxel.

P2, N=120, Active, not recruiting, University of California, Irvine | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

Treatment included IT delivery of cDC1, 6 times weekly, followed by paclitaxel, 80 mg/m2, intravenously, 12 times weekly...In this nonrandomized clinical trial, the addition of IT cDC1 and trastuzumab/pertuzumab before neoadjuvant chemotherapy was well tolerated with manageable adverse effects. Based on safety and immunogenicity, DL2 was selected for the phase 2 dose. ClinicalTrials.gov Identifier: NCT05325632.

P=N/A, N=156, Not yet recruiting, Yunnan Cancer Hospital

In patients with pCR who responded to chemotherapy and dual HER2 blockade (TP), the 3-year RFS and brain metastasis-free survival did not differ according to the type of adjuvant anti-HER2 therapy.

These findings might suggest a potential advantage of nab-paclitaxel combined with trastuzumab and pertuzumab compared with the standard regimen in neoadjuvant therapy for patients with HER2-positive early breast cancer, suggesting that this new combination might establish a new standard for neoadjuvant treatment in this patient population.

P2, N=74, Not yet recruiting, University of Chicago | Initiation date: Jul 2024 --> Jan 2025

P2, N=45, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

This initiative demonstrated the ability to rapidly and effectively transition >95% of eligible breast cancer patients from separate IV trastuzumab and pertuzumab to a fixed combined SC formulation. Patient benefits included shorter administration appointments and a less invasive form of treatment, whereas healthcare system benefits included substantial savings in aseptic preparation time and chair time, and a meaningful increase in clinic capacity. The reported treatment-switch process provides a model that can be adopted by other centres wishing to implement similar treatment switches.

Treatment regimen patterns for HER2-positive BC evolved in correspondence with the U.S. Food and Drug Administration's approval of new drugs for this cancer and National Comprehensive Cancer Network treatment guidelines.

A low baseline SII is associated with better survival outcomes among HER2-positive MBC patients receiving trastuzumab-based first-line therapy.

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.

P3, N=96, Terminated, Hoffmann-La Roche | Completed --> Terminated; Due to low enrollment, the Sponsor decided to prematurely terminate the study

P1, N=55, Active, not recruiting, Bavarian Nordic | Trial completion date: Jun 2026 --> Jan 2025 | Trial primary completion date: Jun 2024 --> Feb 2024

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.

In this study, we analyzed the intrinsic subtype of HR positive, HER2 positive breast cancer based on prediction analysis of microarray 50 (PAM50) and Breast Cancer 360 panel (nanostring) between durable and poor responder in first-line docetaxel + trastuzumab + pertuzumab (THP) treated patients. Conclusions Other than HER2 pathway, ER pathway and inflammatory signal may influence the tumor response of HR(+), HER2 (+) breast cancer. Further clinical trials should be designed based not only on HER2 status, ER status and other molecular subtypes should be considered to maximize the clinical benefit.

Tumors with Ki67 <30 were associated with a lower rate of pCR after completing neoadjuvant treatment. Ki67 was kept as an independent predictor for pCR regardless of the use of neoadjuvant antracycline or trastuzumab plus pertuzumab, and HER2 score as evaluated by IHC. In the future, PAM 50 or another multigenic test may better fit these patients into different prognostic subgroups and help to de-escalate treatment.

For HER2+ aBC (HER2 IHC 3+ or 2+/ISH+), 1L standard of care includes unconjugated HER2 antibodies trastuzumab and pertuzumab (HP) in combination with chemotherapy...For some targeted therapies, including MET inhibitor capmatinib, the magnitude of genomic copy number (CN) gains predict benefit... In a cohort of real-world aBC pts treated with HER2 antibody therapies, HER2 CN ratio was significantly associated with clinical outcomes. For unconjugated antibodies, pts with a HER2 CN ratio of <5 had significantly shorter TTD, PFS and OS. Future work should explore whether these pts may benefit from therapy escalation (e.g.

72 of 84 patients were treated with traditional neoadjuvant chemotherapy plus trastuzumab meanwhile 12 of 84 received neoadjuvant chemotherapy plus trastuzumab and pertuzumab. We would like to acknowledge the contribution of Multispecialistic Biobank Research Core Facilty G-STeP, Fondazione Policlinico Universitario "A. Gemelli" IRCCS (Biobank-FPG) who provided the bioresources.

ESMO Breast 2024) and following T-DM1 monotherapy in the second-line setting or beyond (Brasó-Maristany et al. The HER2DX ERBB2 mRNA score is strongly associated with long-term survival outcomes in metastatic HER2+ breast cancer treated with first-line THP. Notably, HER2DX identified patients with ERBB2-low disease, as the subgroup with the poorest outcomes in both PFS and OS. Further analyses will be presented at the conference.

While immune markers such as TILs and PD-L1 scores are not typically measured in HER2-positive breast cancers, this data opens up the possibility of rationally leveraging targeted therapies in this subset of immune and HER2-sensitive breast cancers, thus potentially avoiding chemotherapy in the future for this biologically selected group. This regimen holds promise as an effective, relatively non-toxic, and biologically-driven alternative to standard chemotherapy for patients with HER2- enriched subset of early breast cancer.

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.