25 april 2022: Bron: Therapeutic advances in Medical oncology First Published March 24, 2022

Een in de klinische praktijk uitgevoerde studie  evalueerde de effectiviteit en veiligheid van pyrotinib bij patiënten met lapatinib - Tykerb resistente HER2-positieve uitgezaaide borstkanker. 
Uit de resultaten blijkt dat bij deze groep van patiénten de behandeling met pyrotinib alsnog bij een aantal patiënten aansloeg en zorgde voor een langere  progressievrije tijd dan alleen met lapatinib. 

Hier een paar grafieken uit de studie. Daaronder het abstract en ook studies bij andere vormen van kanker:




Figure 2. 
Kaplan–Meier analysis of patients who received pyrotinib-based therapy after lapatinib resistance. (a) PFS of all patients who received pyrotinib-based therapy. (b) PFS of patients with brain metastases who received pyrotinib-based therapy.

In deze grafiek hoe patiënten reageerden op de behandeling met pyrotinib.



Summary of pyrotinib-based therapy response in lapatinib-resistant HER2-positive metastatic breast cancer patients.

Klik op de titel van het abstract voor het volledige studierapport:

2022 Mar 24;14:17588359221085232.
 doi: 10.1177/17588359221085232. eCollection 2022.

Treatment with pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer: a multicenter real-world study

Affiliations 
Free PMC article

Abstract

Background: Tyrosine kinase inhibitors (TKIs) are effective for treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, therapies subsequent to TKI progression remain controversial, and effective treatments for TKI resistance are urgently needed. We evaluate the practice of exchange of TKIs, which involves treatment with a different TKI following prior TKI failure. Specifically, this study investigated the efficacy of pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer (NCT04899128).

Methods: This real-world study included 76 patients diagnosed with HER2-positive metastatic breast cancer who received pyrotinib-based therapy after lapatinib progression at four Chinese institutions between August 2018 and March 2020. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and toxicity profiles were reported.

Results: All patients received pyrotinib-based therapy in two or later line therapy. The median PFS was 8.0 months (95% CI 5.1-10.9). OS has not reached. The ORR and CBR were 17.1% and 60.5%, respectively. The median PFS was 7.1 months (95% CI 5.633-8.567) and intracranial ORR was 42.9% in patients who had brain metastasis (n = 14). Patients who benefited from lapatinib ⩾ 6.0 months prior exhibited a longer PFS (10.6 versus 6.0 months, p = 0.034, stratified hazard ratio (HR) 0.534, 95% CI 0.293-0.975). The most common adverse effects were diarrhea (n = 34, 44.7%) and hand-foot syndrome (n = 10, 13.2%).

Conclusion: Pyrotinib-based therapy has the potential to improve survival in patients with lapatinib-resistant HER2-positive metastatic breast cancer, including those with brain metastases. Pyrotinib could provide a clinically significant increase in PFS for patients who benefited from prior lapatinib.

Keywords: breast cancer; human epidermal growth factor receptor 2; lapatinib; metastasis; pyrotinib.

Conflict of interest statement

Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Een vergelijkbare studie is deze, klik op de titel van het abstract. daaronder referenties van eerstgenoemde studie en vergelijkbare studies:

The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study

www.frontiersin.orgD. J Ouyang1,2www.frontiersin.orgQ. T Chen1www.frontiersin.orgM. Anwar1www.frontiersin.orgN. Xie3www.frontiersin.orgQ. C. Ouyang3www.frontiersin.orgP. Z. Fan4www.frontiersin.orgL. Y. Qian5www.frontiersin.orgG. N. Chen1www.frontiersin.orgE. X. Zhou1www.frontiersin.orgL. Guo6www.frontiersin.orgX. W. Gu4www.frontiersin.orgB. N. Ding5www.frontiersin.orgX. H. Yang7www.frontiersin.orgL. P. Liu7www.frontiersin.orgC. Deng8www.frontiersin.orgZ. Xiao6www.frontiersin.orgJ. Li7www.frontiersin.orgY. Q. Wang9www.frontiersin.orgS. Zeng10www.frontiersin.orgShouman Wang6* and www.frontiersin.orgWenjun Yi1*
  • 1Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
  • 2Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
  • 3Department of Internal Medicine of Breast, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
  • 4Department of Breast and Thyroid Surgery, Hunan Provincial People’s Hospital, Changsha, China
  • 5Department of Breast and Thyroid Surgery, Third Xiangya Hospital, Central South University, Changsha, China
  • 6Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, China
  • 7Department of Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
  • 8Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China
  • 9Department of Traditional Chinese Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
  • 10Department of Internal Medicine–Oncology, Xiangya Hospital, Central South University, Changsha, China

Background: Pyrotinib is a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor. Evidence of the efficacy of pyrotinib-based treatments for HER2-positive metastatic breast cancer (MBC) in patients exposed to lapatinib is limited.

Methods: Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC were included in this retrospective study. The primary and secondary endpoints were overall survival (OS) and progression‐free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were implemented to balance important patient characteristics between groups.

Results: Thirty (31.9%) patients were pretreated with lapatinib and subsequently received pyrotinib as an anti-HER2 treatment, and 64 (68.1%) patients did not receive this treatment. The OS and PFS indicated a beneficial trend in lapatinib-naive group compared to lapatinib-treated group in either the original cohort (PFS: 9.02 vs 6.36 months, p = 0.05; OS: 20.73 vs 14.35 months, p = 0.08) or the PSM (PFS: 9.02 vs 6.08 months, p = 0.07; OS: 19.07 vs 18.00 months, p = 0.61) or IPTW (PFS: 9.90 vs 6.17 months, p = 0.05; OS: 19.53 vs 15.10 months, p = 0.08) cohorts. Subgroup analyses demonstrated lapatinib treatment-related differences in PFS in the premenopausal subgroup and the no prior trastuzumab treatment subgroup, but no significant differences were observed in OS.

Conclusion: Pyrotinib-based therapy demonstrated promising effects in HER2-positive MBC patients in a real-world study, especially in lapatinib-naive patients, and also some activity in lapatinib-treated patients.

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