Irene (pyrotinib)

Furthermore, 48 women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC are enrolled to receive neoadjuvant pyrotinib plus chemotherapy (epirubicin-cyclophosphamide followed by docetaxel). In conclusion, neoadjuvant pyrotinib plus chemotherapy has encouraging efficacy and manageable toxicity in women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC. This regimen warrants to be further validated.

P2, N=35, Recruiting, Peking University

P4, N=40, Not yet recruiting, Affiliated Hospital of North Sichuan Medical College; Affiliated Hospital of North Sichuan Medical College

P4, N=40, Not yet recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University

As for a neoadjuvant therapy regimen with Py, an anthracycline-free regimen is feasible. Besides, platinum-containing, long-cycle taxane regimens appear to achieve superior efficacy under anthracycline-removed conditions.

P2, N=140, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Trial primary completion date: Dec 2023 --> Dec 2025

The combination of pyrotinib with metronomic oral etoposide has achieved promising clinical benefits in heavily pretreated HER2-positive MBC, with acceptable and manageable toxicity.

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.

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

No abstract available

These data support further validation in a randomized controlled trial for the assessment of pyrotinib in combination with capecitabine as systemic therapy for patients with HER2-positive breast cancer and brain metastases. National Cancer Center Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.

A population pharmacokinetic model of pyrotinib in HER2 positive breast cancer patients suggested that low serum total protein reduced the clearance rate of pyrotinib in patients. Clinical medical staff should pay attention to the liver function of patients with abnormal serum total protein and be alert to the occurrence of adverse drug reactions.

Our findings underscore the robust synergy between pyrotinib and trastuzumab in overcoming HER2 dependency and provide a rationale for pyrotinib, trastuzumab, and docetaxel as one of the optimal choices for patients with untreated HER2-positive metastatic breast cancer, who are dependent on the HER2 signalling cascade.

For metastatic HER2-positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment, the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy. Therefore, this regimen could be a treatment option for PAM pathway-activated metastatic HER2-positive breast cancer patients.

P3, N=381, Active, not recruiting, Jiangsu HengRui Medicine Co., Ltd. | Recruiting --> Active, not recruiting | N=269 --> 381 | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

P=N/A, N=51, Not yet recruiting, Peking University First Hospital; Peking University First Hospital

P2, N=30, Recruiting, Yongchang Zhang | Trial primary completion date: Dec 2023 --> Dec 2024

Upon irradiation with near-infrared light, ICG generates high levels of intracellular reactive oxygen species and elevated temperature, enhancing chemotherapy effects of pyrotinib. This synergistic action boosts a highly effective anticancer effect promoting the ferroptosis pathway, providing an efficient therapeutic strategy for treating HER2-positive BC.

Due to its optimized antibody-dependent cell-mediated cytotoxicity effect compared with trastuzumab, it has shown good efficacy and safety in the treatment of HER2-positive advanced breast cancer (ABC)...Patients treated with inetetamab plus pyrotinib plus chemotherapy, especially with capecitabine, had the best outcomes (mPFS = 14.0 months)...Inetetamab-based combination therapy shows promising efficacy and good safety in patients with HER2-positive ABC. It is one of the late-line treatment options for Chinese patients with HER2-positive ABC.

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.

Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of EMT regulation via the growth factors pathway, the coronavirus pathogenesis pathway, and vorinostat. The network had RNA-RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-223, mir-25, mir-27, mir-29, and mir-34. The molecular networks revealed in the study may lead to identifying drug targets for GC.

Despite resistance to multiple therapies, including trastuzumab and pertuzumab, the patient exhibited a remarkable therapeutic response to pyrotinib, tegafur combined with radiotherapy. This case provides evidence for the feasibility and potential efficacy of deploying pyrotinib in the salvage treatment of mCRC patients with HER2 amplification even though resistant to other anti-HER2 drugs.

For human epidermal growth factor receptor 2 (HER2)-positive breast cancer, a combination of trastuzumab and pertuzumab regimen were recommended as Level I recommendation for neoadjuvant and first line metastatic breast cancer. Pyrotinib is also recommended as Level I recommendation in first line and second line therapy according to the latest studies conducted in China...There was also a new chapter for HER2-low breast cancer stratified by HR status. We firmly believe that evidence-based, availability-concerned, and consensus-based guidelines will be more feasible for clinical practice in China and in other countries with similar situations.

The patient achieved partial remission and did not show any further progression during the follow-up period. For NSCLC patients with both EGFR mutation and HER2 amplification, the combination of almonertinib and pyrotinib is a valuable therapy that can continuously reduce tumor burden and achieve long-term survival.

P2, N=120, Not yet recruiting, Sun Yat-sen University

Researchers have developed monoclonal antibodies like Trastuzumab and Pertuzumab against HER2 receptors, which have proven highly beneficial in cancer therapy. Bispecific antibodies like Zanidatamab and antibody-drug conjugates like T-DM1 have been developed to overcome the resistance associated with monotherapy. Small molecules such as Lapatinib, Neratinib, and Pyrotinib were initially developed for treating breast cancer...This comprehensive review covers the structural characteristics of HER2, the HER family signaling pathway mechanism, recent findings regarding HER2 receptor involvement in various cancers, and diverse HER2-targeted therapies. This information provides a comprehensive understanding of HER2-targeted strategies in the evolving field of cancer treatment.

The combination of pyrotinib and capecitabine has showed efficacy in these patients. There were no grade 4/5 AEs. Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

This study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.

Hence, the combination of Pyrotinib and Dual HER2 blockade treatment shows promise as a neoadjuvant therapy for locally advanced HER2-positive BC to achieve a pCR in surgery. Nevertheless, this conclusion necessitates additional validation via meticulously designed clinical research investigations encompassing larger patient populations.

P2, N=716, Recruiting, Fudan University | Phase classification: P1/2 --> P2

In this article, we report the case of a patient with HER2+ metastatic breast cancer who developed brain metastases, despite experiencing a durable effect on extracranial metastases after treatment with trastuzumab and pertuzumab. The patient exhibited intracranial progression while receiving treatment with trastuzumab deruxtecan monotherapy after secondary brain radiotherapy and multiple lines of therapy with anti-HER2 agents, such as pyrotinib, lapatinib, tucatinib, and ado-trastuzumab emtansine...The present case indicates that the combination of anlotinib and trastuzumab deruxtecan may be a promising treatment option for patients with HER2+ breast cancer with brain metastasis. Nevertheless, further studies are warranted to verify the present findings.

P=N/A, N=100, Not yet recruiting, Jiangsu Famous Medical Technology Co., Ltd.

This study confirms the promising antitumor activity and acceptable safety of real-world pyrotinib-based regimens for the treatment of HER2-positive MBC patients, particularly those who are trastuzumab-sensitive and who are receiving pyrotinib-based regimens as advanced first-line therapy. It has also been demonstrated that these regimens combined with BRT, provide better intracranial responses and long-term survival benefits for these patients with BM.

In comparison to chemotherapy, HER2-targeted TKIs demonstrated similar activity and PFS benefits for HER2-activating missense mutations in NSCLC.

P2, N=160, Recruiting, the First Affiliated Hospital of Army Medical University; the First Affiliated Hospital of Army Medical University | Not yet recruiting --> Recruiting

P2, N=48, Completed, Sun Yat Sen Memorial Hospital of Sun Yat sen University; Sun Yat Sen Memorial Hospital of Sun Yat sen University | Recruiting --> Completed

P=N/A, N=46, Not yet recruiting, The Fist Affiliated Hospital of Jinzhou Medical University; The Fist Affiliated Hospital of Jinzhou Medical University

P=N/A, N=500, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=65, Recruiting, Shengjing Hospital | Trial completion date: Feb 2029 --> Feb 2030 | Trial primary completion date: Feb 2024 --> Feb 2025

P2, N=109, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is pertuzumab plus trastuzumab and docetaxel as first-line therapy. Comparable results were found for grade ≥3 AE rates of ≥10%. Our results suggest that the pyrotinib and trastuzumab plus docetaxel regimen is most likely to be the optimal first-line therapy for patients with HER2-positive breast cancer.

In the first-line treatment of HER2-Mutant LUAD, regimens involving combinations like chemotherapy + ICIs, chemotherapy + bevacizumab, and pyrotinib may confer enhanced survival advantages compared to chemotherapy. Nevertheless, no significant distinctions were observed among these three treatment strategies, underscoring the imperative to identify biomarkers for the discerning selection of suitable therapeutic modalities. Moreover, patients with suboptimal response to first-line treatment may potentially derive more benefit from pyrotinib.