Dataset Information

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

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.

SUBMITTER: Hua Y

PROVIDER: S-EPMC8958671 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

Hua Yijia Y Li Wei W Jin Nan N Cai Dongyan D Sun Jie J Sun Chunxiao C Yang Fan F Wu Xinyu X Huang Xiang X Wang Biyun B Yin Yongmei Y

Therapeutic advances in medical oncology 20220324

<h4>Background</h4>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 ...[more]

PMID: 35356262

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Project description:Introduction: Combination of trastuzumab (T) and lapatinib (L) has been showed to significantly improve the prognosis of HER2+ heavily pretreated metastatic breast cancer (MBC). Whether TL combined chemotherapy (TLC) can further improve the efficacy in HER2+ MBC remains to be further studied. The aim of the study was to report the first real-world data of TLC in HER2+ MBC, including the efficacy, safety and treatment patterns. Methods: Patients with HER2+ MBC treated with TLC in 5 institutions of China from September 2013 to July 2019 were included. Progression free survival (PFS), objective response rate (ORR), overall survival (OS), toxicity profile and treatment pattern were reported. Results: A total of 285 patients were included. 88.8% were exposed to trastuzumab and 49.2% received 2 or more lines of systematic therapy before TLC previously. The most common chemotherapy regimens combined with TL were capecitabine (40.7%) and vinorelbine (21.4%) and almost 1/3 received maintenance treatment after TLC. Median PFS was 10.9 months while patients received TLC as first line treatment showed longest median PFS of 20.7 months. Patients pretreated with trastuzumab showed a median PFS of 10.2 months. In patients who pretreated with trastuzumab, the continuation of trastuzumab on the basis of standard lapatinib plus capecitabine had a median PFS of 11.3 months. TL combined with capecitabine or vinorelbine showed no significant difference in median PFS, though TL combined with capecitabine had numerically prolongation (11.4 vs. 8.5 months, p = 0.231). Patients had brain metastasis (BM) also showed a median PFS (intracranial and extracranial lesions considered) of 10.6 months. Lines of systematic metastatic treatment was an independent predictive factor of PFS. The median OS was not reached. Two hundred and seventy seven patients were included in ORR analysis. ORR was 42.6%. Toxicities of triplet combinations were tolerable and the most common grade 3 and 4 adverse events were neutropenia (16.8%). Conclusions: TLC demonstrated promising effects and tolerable safety in HER2+MBC, even in patients with BM, providing a theoretical basis for clinical practice. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT04001634.

Project description:IntroductionPyrotinib plus capecitabine has been approved in China for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Meanwhile, vinorelbine is another important chemotherapy option for MBC available in oral and intravenous forms. Thus, pyrotinib plus vinorelbine may represent a new treatment option, particularly for patients with failed capecitabine treatment. This study reported the first real-world data for pyrotinib plus vinorelbine therapy in HER2+ MBC.MethodsHER2+ MBC patients (n = 97) treated with pyrotinib plus vinorelbine in six institutions across China from May 2018 to June 2020 were enrolled. Progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and toxicity profiles were determined.ResultsSixty-seven percent of patients received more than two lines of systematic therapy. Nearly all patients (97.9%) had received trastuzumab and 50.5% were administered lapatinib. When combined with pyrotinib, 74.2% received oral and 25.8% received intravenous vinorelbine. Median PFS (mPFS) was 7.8 (range, 4.7-10.8) months for all patients. The mPFS in patients administered pyrotinib as second-line therapy and third-or-higher-line therapy were 12.0 and 6.4 months, respectively. Patients who received pyrotinib plus oral or intravenous vinorelbine had similar mPFS (7.8 vs. 6.4 months, p = 0.871). The 23 patients with brain metastases had mPFS of 6.3 (range, 3.4-9.2) months. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (10.8 months vs. 5.6 months, p = 0.020). Median OS was not achieved. The ORR for 96 patients was 34.3%. Common grade 3 and 4 adverse events were diarrhea (22.7%), neutropenia (7.2%), and leukopenia (4.1%).ConclusionsPyrotinib plus vinorelbine therapy demonstrated promising effects in HER2+ MBC with tolerable toxicity, particularly in patients with second-line treatment and without prior lapatinib treatment, as well as in patients with brain metastases. Oral vinorelbine is a useful alternative to the intravenous form when combined with pyrotinib.Clinical trial registration[ClinicalTrials.gov], identifier [NCT04517305].

Project description:ObjectivePyrotinib and pertuzumab are effective treatment options for HER2-positive metastatic breast cancer (HER2+ MBC). Our study was to directly compare the efficacy and safety of pyrotinib plus trastuzumab (PyroH) and pertuzumab plus trastuzumab (HP) in patients with HER2+ MBC.MethodsWe conducted a retrospective examination of HER2+ MBC patients who received PyroH plus chemotherapy or HP plus chemotherapy between 2017 and 2022 at five institutions in China. Our primary endpoint was progression-free survival (PFS).ResultsThis study involved 333 patients, among which 161 received PyroH and 172 received HP. The utilization of PyroH as a first-line therapy for MBC was more prevalent among older patients, those with a shorter duration of disease-free interval, or those who had previously been treated with trastuzumab. Although in the first-line advanced treatment HP cohort showed numerically longer PFS (median PFS: 14.46 vs. 22.90 months, p=0.057), in the second-line or later treatments, there was no significant difference in PFS between the PyroH and HP groups (median PFS: 8.67 vs. 7.92 months, p=0.286). Despite HP showing a longer PFS in the overall cohort (median PFS: 9.30 vs. 13.01 months, p=0.005), it did not serve as an independent predictor of PFS in the multivariate analysis (HR 1.134, 95% CI 0.710-1.811, p=0.598). Without taxane, PyroH demonstrated a longer PFS than HP (median PFS: 10.12 vs. 8.15 months, p=0.017). PyroH group displayed a numerically longer median PFS in patients with brain metastases compared to the HP group, though not statistically significant (median PFS: 9.03 vs. 8.15 months, p=0.976). PyroH had higher incidence of grade 3/4 diarrhea (34.3% vs. 3.0%) but similar overall adverse events.ConclusionIn conclusion, PyroH is comparable in second-line or later treatment and during brain metastasis, even having superior efficacy without taxane in real-world setting. Toxicities were tolerable in both groups. (ClinicalTrials.gov: NCT05572645).

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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