In the phase III PHOEBE trial, treatment with pyrotinib plus capecitabine significantly improved overall survival compared with lapatinib plus capecitabine in patients with previously treated HER2-positive metastatic breast cancer.

Kaplan-Meier estimated median OS was 34.9 months (95% CI 28.4-42.1) in P+C group and 23.6 months (95% CI 19.3-34.4) in C-P group (HR 0.74, 95% CI 0.54-1.02; p=0.068). The 2-year OS rate was 65.2% (95% CI 57.6%-71.8%) versus 48.9% (95% CI 38.1%-58.7%), respectively....The updated OS analysis highlighted the long-term efficacy of pyrotinib plus capecitabine in pretreated HER2-positive local relapsed or metastatic breast cancer.

Pyrotinib plus capecitabine significantly improved PFS assessed by investigator compared with that for lapatinib plus capecitabine (12.5 months [95% CI 9.8-13.8] vs 5.6 months [95% CI 5.5-7.0]; HR 0.48 [95% CI 0.37-0.63]; P<0.0001)….With extended follow-up, pyrotinib plus capecitabine demonstrated statistically significant OS improvement compared with lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy.

This is an open-label, randomised, controlled, phase 3 trial done at 29 hospitals in China. Patients with pathologically confirmed HER2-positive metastatic breast cancer...median progression-free survival was significantly longer with pyrotinib plus capecitabine (12·5 months [95% CI 9·7–not reached])...Pyrotinib plus capecitabine significantly improved progression-free survival compared with that for lapatinib plus capecitabine, with manageable toxicity, and can be considered an alternative treatment option for patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy.

At the planned interim analysis, the median PFS was 12.5 months (95% CI 9.7–not reached) with pyrotinib plus capecitabine vs 6.8 months (95% CI 5.4–8.1) with lapatinib plus capecitabine (HR 0.39 [95% CI 0.27–0.56]; P<0.0001), which met the criterion for statistical significance (≤0.0066). Among trastuzumab-resistant pts, prolonged PFS with pyrotinib plus capecitabine was also observed (12.5 months [95% CI 6.9 to not reached] vs 6.9 months [95% CI 5.4 to not reached]; HR 0.60 [95% CI 0.29 to 1.21])...In pts with HER2+ MBC after trastuzumab and chemo, pyrotinib plus capecitabine achieved a significant better PFS than lapatinib plus capecitabine...

A total of 2,104 citations were identified and 12 RCTs comprising 3,769 patients were selected for final analysis....The results indicated that for HER2 positive breast cancer with previous trastuzumab therapy pyrotinib plus capecitabine was probably more efficacious in PFS and ORR.

...Patients were HER2-positive by immunohistochemistry (IHC 3+) or by fluorescence in situ hybridisation (mandatory for IHC2+ tumors); 5. ...

......

...Histopathological examination confirmed invasive breast cancer and HER2 positive; 3. ...

...Pathologically or histologically confirmed HER2-positive breast cancer patients; 3. ...

...HER2 positive advanced breast cancer diagnosed by pathology, cytology or radiology, including inoperable breast cancer with stage IV, or recurrent/metastatic breast cancer. ...

...(1) Signed Informed Consent Form(ICF); (2) Women aged 18 to 75 years; (3) Eastern Cooperative Oncology Group(ECOG) Performance Status 0-1; (4) Expected survival more than 12 weeks; (5) Histologically or cytologically confirmed invasive breast cancer, including locally advanced breast cancer (stage IIIb, stage IIIc) or recurrent and metastatic breast cancer; (6) HER2 positive confirmed by our laboratory tests (HER2 positive definition: IHC 3+ or FISH +); (7) At least one measurable lesion according to RECIST version 1.1 criteria; (8) Disease progress after or during trastuzumab treatment: receive continuous trastuzumab ≥ 2 cycles during relapse/metastasis; or continuous use of trastuzumab ≥ 3 months during adjuvant therapy; (9) Adequate organ function within 7 days prior to the first study treatment: 1) Neutrophil (ANC) >= 1.5x10^9/L, platelet count (PLT) >= 90x10^9/L, hemoglobin >=90 g/L; 2) Serum total bilirubin (TBIL) <= 1.5xthe upper limit of nomal(ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.0xULN, and ALT and AST <= 5xULN in patients with liver metastases; Urea nitrogen (BUN) and creatinine (Cr) <= 1.5xULN; 3) Baseline LVEF >= 50% by ECHO; 4) The QT interval (QTcF) corrected by the Fridericia method is <470 msec....

...Histopathological examination confirmed invasive breast cancer with positive HER2; 3. ...

...Pathological examination confirmed ER and/or PR positive, HER2 positive (ER expression: immunohistochemical staining of tumor cells >= 10%; PR expression: immunohistochemical staining of tumor cells >= 10%; HER-2 positive: immunohistochemical staining 3+ or FISH positive); 5. ...

...Pathologically confirmed HER2-positive invasive breast cancer by local laboratory with the following requirements: HER2 overexpressed or amplified (immunohistochemistry of 3+ or HER2 gene amplification by in situ hybridization) (ISH) positive (ISH amplification rate >= 2.0). ...

......

...Breast cancer with positive HER2 expression confirmed by pathological tests was defined as >10% immunoreactive cells with 3+ immunohistochemical (IHC) fraction or in situ hybridization (ISH) result of HER2 gene amplification (ratio of HER2 basal signal to centromeres 17 signal >= 2.1 or HER2 gene copy number >= 6). ...

...- Histologically confirmed invasive HER2 positive breast cancer;...

...Patients with HER2 positive (defined as documented overexpression or amplification or mutation) metastatic breast cancer who have experienced disease progression following at least 2 prior anti-HER2 therapies for metastatic disease that contain trastuzumab with or without pertuzumab, prior T-DM1, or lapatinib therapy is required; 2....

...For patients with stage IV HER-2 positive breast cancer confirmed by histopathology as recurrence and metastasis or inoperable at the time of diagnosis, HER-2 positive breast cancer was defined as primary or metastatic foci, and HER-2 positive tissue samples were 3 + by immunohistochemistry or + by fluorescence in situ hybridization (FISH); 2. ...

...Breast cancer patients with HER2 positive, low HR (1%-9%) or HR- determined by immunohistochemistry or fluorescence in situ hybridization; 3. ...

...Pathologically confirmed advanced breast cancer patients with positive HER-2 expression; 5. ...

...- Histologically or cytologic confirmed HER2 positive advanced breast cancer which failed prior therapies....

...- Histologically or cytologic confirmed HER2 positive metastatic breast cancer which failed prior therapies....

...- HER2-positive breast cancer(according to 2018 ASCO/CAP HER2 test guideline)....

...Confirmed by pathological examination of breast cancer patients with positive her-2 expression 3....

...Pathologically confirmed HER2-positive invasive breast cancer by local laboratory with the following requirements: HER2 overexpressed or amplified (immunohistochemistry of 3+ or HER2 gene amplification by in situ hybridization) 3....

...Histologically confirmed HER2 positive advanced breast cancer....

...Women aged 18-75 years old; HR positive and HER2 positive (immunohistochemistry or FISH test confirmed)....

...HER2 positive breast cance at any stage; 5....

...HER2 positive recurrent or metastasis breast cancer....

...HER2-positive advanced breast cancer patients diagnosed by pathology or histology; 3. ...

...Early breast cancer patients diagnosed as HER2 positive by pathology or histocytology; 3. ...

...Advanced breast cancer patients with positive her-2 expression confirmed by pathological examination; 3. ...

...Cancer tissue pathology is clearly HER2 positive: including IHC2+/ISH+, IHC 3+ or HER2 mutations (the results obtained by NGS method, PCR method, Sanger method, mass spectrometry sequencing and other measurement methods are all acceptable). ...

...Female patients with HER2-positive breast cancer, aged 18-65 years; 3. ...

...- Enrollment subjects must have a pathological diagnosis of HER2-positive primary invasive breast cancer with an immunohistochemistry (IHC) score of 3 +, or 2 + and HER2 gene amplification by in situ hybridization (ISH) (ratio of HER2/CEP17 ≥ 2.0)....

...Pathologically confirmed HER2 positive, hormone receptor-positive patients with locally advanced or metastatic breast cancer: HER2 IHC 3+, or HER2 IHC 2+ and FISH detection gene amplification, ER（estrogen receptor） and/or PR（progesterone receptor） Immunohistochemical staining of more than 10% tumor cells) 2....

...- Pathologically confirmed HER2 positive breast cancer...

...- Metastatic or locally recurrent HER2-positive breast cancer...

...- HER2 positive: HER2 IHC 3+, or HER2 IHC 2+ and ISH positive -...

...- HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results...

...Positive HER2 expression refers to at least one tumor cell immunohistochemical staining intensity of 3+ or fluorescence in situ hybridization [FISH] in the pathological detection/recheck of the primary or metastatic lesions performed by the pathology department of the participating central hospital confirmed positive; 2....

...Histologically or cytologic confirmed HER2 positive advanced breast cancer which failed prior therapies....

...Histologically or cytologic confirmed HER2 positive advanced breast cancer....

...Patients with HER2+ early or locally advanced breast cancer confirmed by histopathology: HER2-positive is defined by standard of 3+ by immunohistochemical staining (IHC), or 2+ by immunohistochemical staining (IHC) but positive by in situ hybridization (ISH)....

...HER2 positive breast cancer (IHC 3+, or IHC 2+ and FISH positive); lymph node positive, except for T0; lymph node negative and tumor >1cm, or tumor > 0.5 cm and ≤ 1cm, and accompanied by any of the following high-risk factors: pathological grade 3, ER/PR negative, or < 35 years old; 4....

...HER2 positive recurrent or metastasis breast cancer....

...Histologically confirmed HER2 positive...

...HER2-positive breast cancer is confirmed by the pathology laboratory with an immunohistochemical (IHC) score of 3+ and/or 2+ and a positive in situ hybridization (ISH) test (ISH amplification rate ≥ 2.0) 4....

......

...≥18 years old with histologically confirmed HER2 positive breast cancer....

...Histologically or cytologic confirmed HER2 positive metastatic breast cancer....

...immunohistochemical staining of tumor cells ≥ 10%; HER-2 positive: immunohistochemical staining of 3 + or fish positive); 3....

In the case group, the tpCR rate was 63.64% (35/55), the bpCR rate was 69.09% (38/55), and the ORR was 100.00% (55/55). In the control group, the tpCR rate was 39.76% (33/83), the bpCR rate was 44.58% (37/83), and the ORR was 95.18% (79/83). The case group had significantly higher tpCR and bpCR rates than those of the control group...The efficacy and safety of the P + EC-TH regimen were verified by this study. The HER2-positive breast cancer patients treated with the EC-TH neoadjuvant regimen were more likely to achieve tpCR or bpCR if pyrotinib was administered simultaneously.

The confirmed ORR was 79.7% (95% confidence interval [CI], 70.8-88.6), and the CBR was 87.3% (95%CI, 80.0-94.6) in the intention-to-treat population. The pre-specified primary endpoint was met. The median DoR was 15.9 months (interquartile range, 8.3-19.5); the median PFS was 16.0 months (95% CI, 11.2-20.8)...This study demonstrates that pyrotinib plus docetaxel show an acceptable safety profile and promising antitumor activity as a first-line treatment option for patients with HER2-positive MBC.

This study demonstrates that pyrotinib in combination with albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and a manageable safety for patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy.

The ORR of Group A was 54.5% (36/66), while the ORR of Group B was 34.6% (9/26) (P= 0.047). The CBR of Group A was 89.4% (59/66) and that of Group B was 69.2% (18/26) (P= 0.041)….For HER2-positive BC patients with BM, it is recommended to adopt the treatment mode of HFRT combined with pyrotinib, which can improve the local control and survival of patients.

Thirty-five deaths occurred, and the estimated median overall survival (OS) was 41.7 months (95% CI, 32.2-not reached). Subgroup B (n=49) had the longest median OS (41.7 months) and PFS (17.8 months)….The updated OS analysis highlights the long-term efficacy of pyrotinib plus capecitabine in HER2-positive advanced breast cancer patients who have shown primary resistance to trastuzumab.

The pathological and clinical data of 77 HER2-positive advanced breast cancer patients treated with pyrotinib after prior trastuzumab and pertuzumab were retrospectively analyzed….The median PFS was 13.6 months (95%CI: 8.3-18.9). The ORR was 50.0% in the 56 patients with evaluable lesions,the CBR was 54.5%, and the mPFS was 10.8 months (95%CI: 7.7-13.9). 46 patients who progressed on prior trastuzumab and pertuzumab had evaluable lesions, the ORR was 43.5%, CBR was 69.6%, and the mPFS was 9.2 months (95%CI: 6.4-12.0)....This study first retrospectively analyze the value of pyrotinib in the era of dual anti-HER2 therapy, preliminarily showing good efficacy and safety of pyrotinib in patients after prior trastuzumab and pertuzumab.

The median PFS of TKIs-based therapy was 11.9 months (95% CI 7.9-15.9). ORR and CBR were 19.6% and 72.5%, respectively. A median PFS of 10.5 months (95% CI 7.5-13.5) and an intracranial ORR of 33.3% were observed among patients with brain metastasis (n=12). A better PFS was observed among patients with pyrotinib (n=21) compared with lapatinib (n=30), and patients who derived favorable benefit from T-DM1 (PFS ≥ 6 months)....TKIs-based therapy showed promising efficacy and safety in patients with HER2-positive MBC after T-DM1 failure, including those with brain metastases.

The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3-27.2), and the median PFS was 6.4 months (95%CI, 4.0-8.8). The ORR was 43.6% (95% CI, 27.8%-60.4%) and the DCR was 84.6% (95% CI, 69.5%-94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (P=0.017)....Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

At a median follow-up of 17.3 months, 1-year CNS-PFS rate was 74.9% (95% CI 61.9-90.7%) and median CNS-PFS was 18 months (95% CI, 15.5 to NA months). One-year PFS rate was 66.9% (53.1-84.2%) and median PFS time was 17.6 months (95% CI 12.8-34.1 months). The best intracranial response rate (IC-ORR: complete response and partial response) was 92.5% (37/40)....Radiotherapy combined with pyrotinib and capecitabine resulted in a promising efficacy that crossed the pre-specified boundary in patients with HER2-positive advanced breast cancer with brain metastases.

HER2 positive patients received oral metronomic capecitabine 500 mg three times a day and pyrotinib 400 mg per day….The median PFS and OS was 11.9 months (95%CI 8.8-14.6) and 29.3 months (95%CI 24.4-34.8) respectively. ORR was 34.7%, and CBR was 81.6% with 2 CR (4.1%), 15 PR (30.6%) and 23 SD (46.9%). The mPFS in first- or second-line treatment was 12.2 months....The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2 positive metastatic breast cancer patients.

Progression-free survival (PFS), OS, objective response rate, and safety were analyzed following the administration of pyrotinib….In 61 patients with BM, the median PFS was 7.50 months, the median central nervous system (CNS)-PFS was 11.17 months, and the median OS was 21.27 months....Long-term outcomes of pyrotinib-based therapy are promising for patients with HER2-positive metastatic breast cancer in real world and in patients with BM, regardless of the treatment lines and prior anti-HER2 therapies.

The median PFS was 11.8 months (95% confidence interval [CI], 8.4–15.1), which crossed the pre-specified efficacy boundary of 8.0 months. The objective response rate was 70.0% (70/100), with a median duration of response of 13.8 months (95% CI, 10.2–19.3). The disease control rate was 87.0% (87/100)....Pyrotinib plus capecitabine can be considered to be a treatment option in HER2-positive advanced breast cancer patients who have shown primary resistance to trastuzumab.

Short-term efficacy showed that 4 cases of complete remission (CR), 61 cases of partial remission (PR), 23 cases of stable disease (SD) and 3 cases of progression disease (PD) were identified, and the ORR, DCR and CBR were 71.4%, 96.7% and 74.7%, respectively....Pyrotinib-based regimens were safe and effective in the treatment of HER2-positive advanced breast cancer, and the earlier use was better. Pyrotinib-based therapy might have some advantages in patients without liver metastases.

The results of the present study demonstrated that the median PFS (mPFS) was 8.1 months for all patients, ranging from 3.3‑10.6 months. Patients receiving pyrotinib as second‑line therapy exhibited a longer mPFS of 8.5 months compared with those receiving it as third‑ or higher‑line therapy (mPFS, 5.9 months)....Collectively, the results of the present study indicated that pyrotinib‑based treatment is effective for patients with HER2+ ABC, including those who have previously been treated with trastuzumab. Thus, the combination of pyrotinib with albumin‑bound paclitaxel is recommended due to high levels of efficacy, convenience and tolerability.

Patients with BM of HER2-positive MBC (n=35) treated with pyrotinib-containing therapy were enrolled in this analysis….The median PFS time was 8.00 (95%CI, 5.98–10.017) months and the median OS time was 23 (95%CI, 10.412–35.588) months. The ORR was 45.7% and the DCR was 74.3%....Pyrotinib-containing therapy shows favorable effectiveness and tolerable safety in patients with BM of HER2-positive MBC, particularly in population with brain radiotherapy-naive, received pyrotinib as first or second-line treatment, and developed supratentorial brain metastasis.

The 1-year and 3-year OS rates were 78.9% (95% CI: 64.0-99.6) and 29.1% (95% CI: 13.0-60.4), respectively….These findings suggest the long-term survival benefit provided by pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases, especially in the radiotherapy-naive cohort.

The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2-positive metastatic breast cancer patients.

Median CNS PFS was 10.0 months (95% CI, 5.3-14.7). CNS objective response rate was 100%, including two (11%) patients with CNS complete response. Median overall PFS was 8.5 months (95% CI, 4.8-12.2). Median overall survival was 19.0 months (95% CI, 13.1-24.9)...Radiotherapy combined with pyrotinib plus capecitabine shows favorable CNS response and promising survival outcomes in patients with HER2-positive metastatic breast cancer and untreated symptomatic brain metastases, with an acceptable safety profile.

Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.

The median PFS was 8.2 months in the pyrotinib monotherapy cohort and 22.1 months in the pyrotinib plus capecitabine group, while the median OS was 27.1 months in the pyrotinib monotherapy group and 37.4 months in the pyrotinib plus capecitabine group….The updated survival results based on individual patient data from the phase I trials of pyrotinib-based regimen revealed promising PFS and OS in HER2-positive MBC.

The objective response rate (ORR) of 37 patients was 97.3%. Two patients reached clinical complete response, 34 obtained clinical partial response, 1 sustained stable disease, and no one had progressive disease….The regimen of 4 cycles of EC combined with pyrotinib presented some feasibility in the neoadjuvant setting for HER2-positive breast cancer with manageable safety.

Pyrotinib combined with chemotherapy is superior to lapatinib combined with chemotherapy among HER2+ metastatic breast cancer patients, with a significant improvement in PFS (prior trastuzumab therapy) (HR: 0.47, 95% CI: 0.39-0.57, p<0.001, I2 = 0%, FEM), PFS (trastuzumab resistance) (HR: 0.52, 95% CI: 0.39-0.68, p<0.001, I2 = 40%, FEM) and ORR (RR: 1.45, 95% CI: 1.26-1.67, p<0.001, I2 = 8%, FEM)...The efficacy of pyrotinib combined with chemotherapy is superior to lapatinib combined with chemotherapy but has more safety risks.

Total ORR and CBR of the whole group was 37.8% and 77.8%, respectively. There were 14 patients with brain metastases (31.1%), with a median PFS of 6.8 months (95% CI: 5.4~9.8)….Pyrotinib is safe and effective for elderly patients with advanced HER2 positive BC.

Current study included 61 HER2-positive BC patients with brain metastases (BM) who were treated by pyrotinib-based regimens….Pyrotinib-based systemic therapy resulted in 8.6 months median PFS (mPFS) and 18.0 months median OS (mOS) among the BM patients....Pyrotinib-based combination therapy is safe for HER2-positive brain metastasis treatment. Compared with vinorelbine or capecitabine, pyrotinib combined with nab-paclitaxel is more effective with less toxicity, which is the preferable regimen for HER2-positive brain metastasis.

The ORR and CBR were 45.1% and 81.5%, respectively. A significantly longer PFS was reported in patients who received pyrotinib as first-line treatment...This study further demonstrated the outstanding efficacy and safety of pyrotinib and reported the potential predictors of survival in HER2+ ABC.

The confirmed ORR in 79 patients was 77.2% (95% CI, 66.4%-85.9%); 3 patients achieved CR and 58 achieved PR. The confirmed ORR in the per-protocol set (n=79) was 79.2% (95% CI, 68.5%-87.6%)….Pyrotinib in combination with docetaxel exhibits promising antitumor activity and acceptable safety profile among patients with HER2-positive metastatic breast cancer in the first-line setting.

The median progression-free survival (mPFS) of 172 patients was 8.83 months….Among 146 patients evaluated for efficacy, 2.1%, 58.9%, and 32.9% showed complete response, partial response, and stable disease, respectively….Pyrotinib-containing regimen could effectively treat HER2-positive MBC with acceptable toxicity, including the patients who progressed after lapatinib treatment and with brain metastasis.

A total of 27 HER2+ breast cancer patients received neoadjuvant pyrotinib plus TAC...Regarding pathological response, there were 1 (2.7%), 3 (11.1%), 8 (29.6%), 5 (18.5%), and 10 (37.0%) patients realizing Miller-Payne grade (G) 1, G2, G3, G4, and G5, respectively; besides, 10 (37.0%) patients achieved total pathological complete response (pCR), 10 (37.0%) patients realized pCR in breast, and 23 (85.2%) patients achieved pCR in lymph node....Neoadjuvant pyrotinib plus TAC treatment is efficient and safe in HER2+ breast cancer patients, while further validation is needed.

Compared with EC-TH along (37.5%, 3/8), the addition of pyrotinib to EC-TH neoadjuvant chemotherapy (py+EC-TH) significantly increased the pathological complete response (pCR)rate (75%, 9/12) in patients with HER2-positive breast cancer. The objective response rate (ORR) was 87.5% (7/8) vs 100% (12/12)....Pyrotinib added to EC-TH neoadjuvant therapy significantly increased the pCR rate, suggesting an applicable strategy for HER2-positive breast cancer.

Among 38 evaluable patients, four patients (10.5%) had CR, 27 (71.1%) had PR, six (15.8%) had stable disease, and one (2.6%) had progressive disease. The confirmed ORR was 81.6% (95% CI 65.1-91.7%). Pyrotinib combined with nab-paclitaxel showed a promising antitumor activity with good tolerance in patients with HER2-positive advanced or metastatic breast cancer.

The median PFS (mPFS) was 14.23 months (95% CI 8.13-20.33). The ORR and DCR were 38.9% and 83.3%, respectively. Pyrotinib combined with metronomic oral vinorelbine showed promising efficacy and manageable safety in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy.

...we analyzed 171 patients with HER2+ ABC, who received pyrotinib-based treatment...Patients receiving pyrotinib as first-line treatment demonstrated a significantly longer PFS than those who received pyrotinib as second-line or beyond treatment (13.0 months vs. 10.7 months, p=0.020)....Pyrotinib dramatically improved the clinical outcomes of HER2+ ABC with imaginable toxicities, especially for patients who received first-line treatment and had the ECOG-PS of 0-1, as well as those who were lapatinib-naive.

This real-world study included 76 patients diagnosed with HER2-positive metastatic breast cancer who received pyrotinib-based therapy after lapatinib progression...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)....Pyrotinib-based therapy has the potential to improve survival in patients with lapatinib-resistant HER2-positive metastatic breast cancer, including those with brain metastases.

We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases. The intracranial objective response rate was 74·6% (95% CI 61·6–85·0; 44 of 59 patients) in cohort A and 42·1% (20·3–66·5; eight of 19 patients) in cohort B.

A total of 20 such patients were separated into pyrotinib plus capecitabine and capecitabine-only groups in a 1:1 ratio. All patients met either the primary or secondary endpoints. Oral admission of pyrotinib together with radiotherapy can significantly increase the overall response rate, progression-free survival, time to progression and duration of response of HER2+ brain metastatic breast cancer patients, without causing extra adverse events.

This is a retrospective observational study including lapatinib-resistant HER2-positive MBC patients who received pyrotinib-based treatment....The objective response rate (ORR) was 25.8% and the median progression-free survival in the study population was 4.5 months (95% CI: 3.1-5.9 months)....Pyrotinib-based treatment was effective and generally well tolerated in lapatinib-resistant HER2-positive MBC for later line treatment.

The objective response rate (ORR) and disease control rate (DCR) of central nervous system (CNS), were found in 20 of 42 (47.6%) and in 39 of 42 (92.8%), respectively, while for extra-CNS, the respective ORR and DCR were in 9 of 38 (23.6%) and in 36 of 38 (94.7%), respectively....Pyrotinib combined with chemotherapy/radiotherapy or alone showed significantly greater local control rates and progression free survival (PFS), with manageable toxicity for patients with HER2-positive breast cancer with brain metastases, and further follow-up will provide an overall survival (OS) data.

Neoadjuvant pyrotinib combined with the TAC regimen showed promising clinical benefit in patients with HER2-positive locally advanced breast cancer, with an acceptable safety profile.

...treatment data of HER2-positive mBC patients receiving pyrotinib-based treatment from August 2018 to July 2019 in Qilu Hospital of Shandong University and other medical centers of Shandong Province in China....Pyrotinib is highly beneficial to HER2-positive metastatic breast cancer patients, even in patients with previous lapatinib exposure.

The objective response rate (ORR) of all patients was 73.4%, and the disease control rate (DCR) was 98.4%, with a clinical benefit rate (CBR) of 87.5%. Pyrotinib is highly beneficial to HER2-positive metastatic breast cancer patients...

This was a China-based, prospective, real-world, observational cohort study. HER-2 Positive MBC Patients treated with pyrobitinib were indentified from the Breast Cancer Information Management System between 2017/06 and 2020/09. Treatment outcomes assessment included provider-reported objective response rate (ORR), progression-free survival (PFS) and overall survival (OS)....Compared with phase II and phase III clinical trails of pyrotinib, our real-world data showed simiar clinical effectiveness in HER-2 positive MBC patients and, in particular, improved outcomes in patients with brain metastasis.

In this retrospective study, 275 patients who received pyrotinib-based therapy for HER2-positive metastatic breast cancer from 12 institutions between March 2019 to August 2020 were initially included….Among patients with HER2-positive metastatic breast cancer, pyrotinib-based therapy demonstrated encouraging effects and acceptable tolerability in the real-world setting.

Pyrotinib in combination with docetaxel exhibits promising antitumor activity and acceptable safety profile among patients with HER2-positive metastatic breast cancer in the first-line setting. Loperamide prophylaxis is an effective approach for the prevention of diarrhea.

The combination of pyrotinib and fulvestrant was convenient and effective with manageable toxicity, which may offer a chemotherapy-free alternative treatment option for patients with HR+/HER2+ metastatic breast cancer.

Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC...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.

...168 patients with HER2+ MBC….Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants….Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort.

mPFS in patients receiving regimen with and without capecitabine were 15.1 months and 8.4 months, respectively (P= 0.081)....Pyrotinib demonstrated an encouraging efficacy and manageable safety in patients with advanced HER2+ breast cancer.

Patients with histologically confirmed advanced HER2 positive breast cancer were included in the analyses...mPFS in patients receiving regimen with and without capecitabine were 15.1 months and 8.4 months, respectively (P= 0.081)...Pyrotinib demonstrated an encouraging efficacy and manageable safety in patients with advanced HER2+ breast cancer.

Pyrotinib plus capecitabine resulted as an effective and safe treatment for HER2-positive BC patients…

These results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane.

...66 (86.8%) patients received pyrotinib immediately after lapatinib and 10 (13.2%) received pyrotinib...Objective response rate (ORR) was 17.1%, and clinical benefit rate (CBR) was 60.5%. Patients who benefited from lapatinib ≥6.0 months were found to have a longer PFS (P=0.034; stratified hazard ratio [HR] 0.534, 95%CI 0.293-0.975)...Pyrotinib could improve the survival of HER2-positive metastatic breast cancer patients after the failure of lapatinib.

Ten HER2 amplification-negative, mutation-positive patients who received pyrotinib monotherapy were ultimately included in the efficacy analysis. The median PFS was 4.9 months. The objective response rate (complete response + partial response) was 40.0% and the clinical benefit rate (complete response + partial response + stable disease over 24 weeks) was 60%....Patients with HER2-mutated, non-amplified metastatic breast cancers may benefit from pyrotinib.

The patients received 320 mg pyrotinib orally once per day for 21 days plus standard chemotherapy (pyrotinib+TCH) with six 21-day cycles of docetaxel (75 mg/m2) plus carboplatin (6 mg/mL/min) and trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose)....The current trial suggests that pyrotinib plus trastuzumab-based standard chemotherapy has promising efficacy and manageable toxicity in patients with HER2-positive early breast cancer in a neoadjuvant…

Pyrotinib plus capecitabine resulted as an effective and safe treatment option for asymptomatic HER2-positive BC patients with low-volume brain metastases who were not treated with radiotherapy.

13 patients with HER-2 positive advanced solid tumors were enrolled, including 11 patients with metastatic breast cancer, 3 patients with metastatic colon cancer, 3 patients with gastric cancer. Among them, 10 patients were evaluated for efficacy and(or) side effect, of which 3 patients were excluded because they were not taken pyrotinib according to the medical order... The total mPFS was 5.63 months (95%CI: 2.533-5.467), partial remission (PR) were 3 cases(30%), stead diease(SD) were 6 cases(60%), progress diease was 1 case(10%). The overall response rate (ORR) and the disease control rate (DCR) were 23.1%, 69.2%, respectively....The treatment of HER-2 positive advanced solid tumors with pyrotinib have good exact effect, and the toxicity could be controlled.

The PFS was significantly prolonged with pyrotinib plus capecitabine vs lapatinib plus capecitabine (median, 12.4 months [95% CI, 11.1 months to not reached] vs 8.2 months [95% CI, 5.5 to 9.7 months]; hazard ratio, 0.40 [95% CI, 0.25 to 0.66]; p = 0.0001). The ORR was 71.4% (95% CI, 60.5% to 80.8%) with pyrotinib plus capecitabine compared with 58.1% (95% CI, 44.8% to 70.5%) with lapatinib plus capecitabine.

Pyrotinib is highly beneficial to second-or-higher-line patients or HER2-positive MBC patients with brain metastases.

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)...Pyrotinib 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.

The PFS tended to be prolonged with pyrotinib plus capecitabine vs lapatinib plus capecitabine (median, 12.4 months [95% CI, 6.9 to not reached] vs 6.9 months [95% CI, 5.5 to not reached]; hazard ratio, 0.62 [95% CI, 0.31 to 1.24]; p=0.0864). The objective response rate was 67.4% (95% CI, 51.5% to 80.9%) with pyrotinib plus capecitabine compared with 54.5% (95% CI, 36.4% to 71.9%) with lapatinib plus capecitabine...Pyrotinib plus capecitabine showed favorable efficacy in pts with HER2-positive, trastuzumab-resistant relapsed or metastatic breast cancer.

105 patients were enrolled in the pyrotinib group (n=55) or T-DM1 group (n=50)...The median PFS was 6.0 months (95% CI, 4.7 to 7.3 months) with pyrotinib and 4.2 months (95% CI, 3.6 to 4.8 months) with T-DM1 (P=0.044)….The results of this study suggest that patients with HER2-positive MBC with trastuzumab and lapatinib failure can benefit from subsequent pyrotinib treatment and tolerate this treatment well, especially those who have benefited from previous lapatinib treatment or those who have no liver metastasis.

We report a 56-year-old Chinese woman with breast cancer (cT3N1MX, Her-2+/HR-)….The clinician prescribed the regimen (pyrotinib 320mg qd + capecitabine 1g bid D1-D14 Q3W). The tumor was significantly reduced after 1 month of single administration of pyrotinib, and partially relieved after 2 months of pyrotinib + capecitabine. The main side effects were grade II hand foot syndrome and grade II diarrhea. This case shows that the combination of pyrotinib and capecitabine has potential therapeutic benefits in HER-2+ breast cancer patients with end-stage renal disease.

Here we report five cases of HER2-positive BC patients with severe cutaneous metastases. All patients received treatments containing pyrotinib and got a rapid treatment response with a remarkable disease-free time. This finding suggests that pyrotinib has good potential as a treatment option for patients with BC cutaneous metastases.

CONTRADICTING EVIDENCE:...she was diagnosed with HER-2 positive breast cancer... Given the patient’s disease progression, liver metastasis was diagnosed and she underwent two cycles of chemotherapy with with pyrotinib and capecitabine.

The woman was diagnosed with invasive carcinoma of the left breast and lymph nodes and lung nodules metastasis. The patient received 6 cycles of pyrotinib in combination with capecitabine regularly. Progression free survival was more than 6 months, and the patient's efficacy evaluation was partial remission. Our clinical observations demonstrated that pyrotinib may be an effective treatment for patients with HER2-positive MBC.

...we report pyrotinib combined with carboplatin in treating a patient with HER2-positive relapsed breast cancer who had acquired resistance to trastuzumab...The patient showed an excellent response to the therapy...Our case provides evidence for the feasibility and efficacy of pyrotinib with carboplatin in treating patients with HER2-positive relapsed or metastatic breast cancer who may develop resistance to trastuzumab.

In this study, we aimed to investigate the antitumor efficacy of pyrotinib combined with adriamycin (ADM) and explore its mechanisms on HER2+ breast cancer...These findings suggest that the combination of PYR and ADM shows synergistic effects both in vitro and in vivo.

Moreover, in vivo experiments demonstrated that pyrotinib in combination with 5-FU more effectively inhibited SKBR-3/FU tumor growth than either pyrotinib or 5-FU alone.