INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

As a newly emerged class of anticancer bioagents in the most precise and selectively targeted way, antibody-drug conjugate (ADC) combines the cancer-targeting abilities of monoclonal antibodies with the cytotoxicity potency of payload, delivering highly cytotoxic drug into tumors via 'targeted chemotherapy'. ADC has revolutionized the treatment landscape of human epidermal growth factor receptor 2 positive and triple negative subtypes in breast cancer. Three ADCs have been approved by U. S. Food and Drug Administration with breast cancer indications, including trastuzumab emtansine (T-DM1; also approved in China), trastuzumab deruxtecan (T-DXd, DS-8201) and sacituzumab govitecan (IMMU-132; also approved in China). Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class. For example, more attention should be paid to the management of thrombocytopenia, hepatotoxicity, and reductions in left ventricular ejection fraction (LVEF) in patients treated with trastuzumab emtansine; clinical physicians should pay attention to the risk of neutropenia, interstitial lung disease/pneumonitis, and reductions in LVEF when treated with trastuzumab deruxtecan; sacituzumab govitecan most frequently caused neutropenia, anemia and diarrhea requiring close monitor. ADC has generally favorable safety profiles, and dose modifications and/or symptomatic supporting treatment are effective in terms of toxicity management. This consensus aims at providing guidance for clinical oncologists of early detection, regular assessment, timely management and follow-up monitor of ADC-associated adverse reactions/events.
Ado-Trastuzumab Emtansine/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Breast Neoplasms/therapy* ; Camptothecin/adverse effects* ; Consensus ; Cytotoxins/therapeutic use* ; Female ; Humans ; Immunoconjugates/therapeutic use* ; Neutropenia/etiology* ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/therapy* ; Ventricular Function, Left

OBJECTIVETo evaluate the efficacy and safety of trastuzumab plus different chemotherapy regimens in treatment of patients with HER-2-positive advanced breast cancer.

METHODS132 patients with advanced HER-2-positive breast cancer were treated with trastuzumab plus different regimens. The clinical characteristics, efficacy and toxicity of the 132 patients were retrospectively analyzed.

RESULTSFive patients had complete response (CR), 61 patients had partial response (PR), 39 patients had stable disease (SD), and 27 patients had progressive disease (PD). The objective response rate was 50.0% and the disease control rate was 79.5%. The median progression-free survival was 9.3 months. The median overall survival time was 46.2 months. The 1-, 2-, 5- year survival rates were 98.3%, 81.9% and 40.2%, respectively. Trastuzumab combined with chemotherapy is superior to trastuzumab monotherapy (51.2% vs. 33.3%). The number of metastatic sites, efficacy, different previous treatment lines were independent prognostic factors of PFS (P = 0.002, P < 0.0001 and P < 0.0001, respectively). Visceral metastases, pathological grade, and PFS were independent prognostic factors of OS (P = 0.041, P = 0.001, P = 0.025, P < 0.001, P < 0.0001 and P < 0.0001, respectively). Regarding the toxicities, one case discontinued treatment due to the decrease of left ventricular ejection fraction to 47%, two cases had heartbeat tachycardia, 6 cases had palpitation, 17 cases had a fever during first input trastuzumab. No other serious cardiac toxicity was observed. The most common toxicities were chemotherapy-related hematological and non-hematological toxicities.

CONCLUSIONSTrastuzumab combined with chemotherapy is superior to trastuzumab monotherapy. Patients may get benefits for early use of trastuzumab. Trastuzumab plus chemotherapy is effective and well tolerated in patients with advanced HER-2 positive breast cancer. No heart failure occurred in this series of patients, and cardiac safety seems better than that in Caucasians because of younger age at the onset in Chinese advanced breast cancer patients.

Adult ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; Disease Progression ; Disease-Free Survival ; Female ; Fever ; chemically induced ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neutropenia ; chemically induced ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Survival Rate ; Taxoids ; administration & dosage ; Trastuzumab ; Vinblastine ; administration & dosage ; analogs & derivatives ; Vomiting ; chemically induced

OBJECTIVETo evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma.

METHODSTwenty consecutive cases of chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma treated in Peking University Cancer Hospital between 2009 June and 2013 August were included in this study. The patients with adenocarcinoma were previously confirmed and were eligible if their tumor showed overexpression of HER-2+++ by immunohistochemistry or HER-2 gene amplification-positive by FISH, and if they failed to at least one previous chemotherapy. Response and toxicities were evaluated with RECIST 1.0 and CTC AE 3.0 criteria.

RESULTSThe twenty patients received trastuzumab plus second- or later-line chemotherapy, consisting of nine platinum with fluoropyrimidines, five paclitaxel with fluoropyrimidines, three fluoropyrimidines monotherapy, two irinotecan monotherapy, and one docetaxel monotherapy. In these 20 cases, 3 PR (15.0%) and 10 SD (50.0%) were achieved, with a disease control rate of 65.0%. The median PFS was 6.1 months (95%CI 3.0-9.2) and median OS was 11.1 months (95%CI 8.4-13.7). The median cycle number of Trastuzumab administration was 6.5. The patients treated with Trastuzumab ≥ 6 times had a median OS of 13.8 months, significantly longer than that of 9.5 months in the patients treated <6 times (P < 0.001). The patients treated with Trastuzumab ≥ 6 times had a median PFS of 7.8 months, significantly longer than that of 3.7 months in patients treated <6 times (P = 0.029). Among the 20 cases, loss of appetite (13 cases of grade 1-2), neutropenia (12 cases of grade 1-2 and 3 cases of grade 3-4) and fatigue (9 cases of grade 1-2 and 3 cases of grade 3-4) were the most frequent adverse events. No cardiac events including asymptomatic decreases in LVEF ≥ 10% and no treatment-related death were recorded.

CONCLUSIONSCombination of trastuzumab with chemotherapy is effective and safe in patients with HER2-positive advanced chemo-refractory gastric or gastro-esophageal junction adenocarninoma. However, prospective studies are warranted to further confirm its efficacy and safety.

Adenocarcinoma ; drug therapy ; metabolism ; secondary ; surgery ; Adult ; Aged ; Anorexia ; chemically induced ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Cisplatin ; administration & dosage ; adverse effects ; Disease Progression ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Esophagogastric Junction ; Fatigue ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; adverse effects ; Pyrimidines ; administration & dosage ; adverse effects ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; metabolism ; secondary ; surgery ; Survival Rate ; Trastuzumab

OBJECTIVETo evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

METHODSFifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.

RESULTSEighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.

CONCLUSIONSAddition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

Aged ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; China ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Esophageal Neoplasms ; drug therapy ; pathology ; Esophagogastric Junction ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Neutropenia ; chemically induced ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; pathology ; Survival Rate ; Trastuzumab ; Vomiting ; chemically induced

OBJECTIVETo assess the efficacy and safety of neoadjuvant 3-weekly paclitaxel plus trastuzumab (TH) in Chinese women with Her-2 overexpressing operable breast cancer.

METHODSThis is a single center open-label phase II clinical trial. The included patients underwent 4 cycles of neoadjuvant 3-weekly TH before surgery. The primary endpoint was pathologic complete response rate (pCR rate) and the secondary endpoint was overall response rate (OR rate). Patients were also stratified according to hormone receptor status, and pCR rate and OR rate were compared between subgroups. Adverse events were graded according to CTCAE v3.0.

RESULTSThere were 40 eligible patients entering this study with median age of 49 years. All patients completed 4 cycles of neoadjuvant treatment. pCR rate was 52.5% and OR rate was 87.5%. The differences of pCR and OR rates between subgroups were of no statistical significance. No cardiac toxicity event severer than grade 2 was recorded.

CONCLUSION3-weekly TH regimen has satisfactory pCR rate and OR rate in Chinese patients with Her-2 overexpressing operable breast cancer and reliable safety.

Adult ; Antibodies, Monoclonal ; administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asian Continental Ancestry Group ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Trastuzumab

OBJECTIVETo evaluate the efficacy and toxicity in patients with HER2 overexpressing metastatic breast cancer.

METHODSTwenty-one patients with HER2 overexpressing metastatic breast cancer entered into the study. Trastuzumab (8 mg/kg day 1, then 6 mg/kg every 21 days or 4 mg/kg, then 2 mg/kg every week) and vinorelbine (25 mg/m(2)) was given on days 1 and 8 every 21 days.

RESULTSOverall 56 cycles were given to the 21 patients enrolled into the study (mean 2, range 1-6). All can be evaluated. The response rate was 33.33% (7/21), one patient achieved complete response (CR), six patients achieved partial response (PR), four patients achieved stable disease (SD), ten patients achieved progressive disease (PD)]. The median time to progression was 3.5 months. One year overall survival was 33%. The major toxicity was myelosuppression and peripheral neuritis. A few patients were observed with fever and lower grade cardiac failure.

CONCLUSIONThe combination of trastuzumab and vinorelbine is an effective and well tolerated therapy in patients with pretreated metastatic breast cancer.

Adult ; Aged ; Anemia ; chemically induced ; Antibodies, Monoclonal ; administration & dosage ; adverse effects ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; Female ; Humans ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Metastasis ; Receptor, ErbB-2 ; metabolism ; Survival Analysis ; Thrombocytopenia ; chemically induced ; Trastuzumab ; Treatment Outcome ; Vinblastine ; administration & dosage ; adverse effects ; analogs & derivatives ; Vomiting ; chemically induced

OBJECTIVETo investigate the efficacy and toxicity of recombinant humanized anti-Her-2/neu antibody (Herceptin) and Taxol for patients with Her-2/neu overexpressing metastatic breast cancer.

METHODSSixty patients with Her-2/neu overexpressing metastatic breast cancer were investigated. Of the 60 cases, 22 were treated with Herceptin and Taxol and 38 with Taxol and doxorubicin.

RESULTSThe total response rate (RR) of Herceptin and Taxol was 68.2%, and that of Taxol and doxorubicin was 44.7%. The RR of patients with Her-2/neu(+++) was 75%, while that of patients with Her-2/neu(++) was 50%. The major adverse effects were gastro-intestinal tract reactions, myopathy, bone marrow suppression and alopecia.

CONCLUSIONThe treatment with Herceptin and Taxol is effective and safe for patients with Her-2/neu overexpressing metastatic breast cancer. The therapeutic effect is related to the degree of Her-2/neu overexpression.

Adult ; Aged ; Antibodies, Monoclonal ; administration & dosage ; adverse effects ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; chemistry ; drug therapy ; Female ; Humans ; Middle Aged ; Paclitaxel ; administration & dosage ; adverse effects ; Receptor, ErbB-2 ; analysis ; Trastuzumab

OBJECTIVETo evaluate the efficacy and adverse reactions of Herceptin as a single agent in patients with HER2 overexpressing metastatic breast cancer.

METHODSThere were two kinds of therapy protocol. One was loading-dose of 4 mg/kg intravenously, followed by a 2 mg/kg maintenance dose of weekly intervals. The other was loading-dose of 8 mg/kg, followed by 6 mg/kg of every three weeks intervals.

RESULTSAmong 20 patients with evaluated efficacy, there was no complete response, 5 patients (25.0%) showed partial response (PR), 5 (25.0%) stable disease (SD) and 10 (50.0%) progressive disease (PD). Of 22 patients, the overall response rate was 22.7%. The median time of disease progression and treatment failure was 6 weeks and 6.5 weeks, respectively. The most common adverse reactions were fever and chill. Cardiac symptoms could be seen in some patients.

CONCLUSIONHerceptin is an active agent for the patients with HER2 overexpressing metastatic breast cancer and the adverse events are well tolerated.

Adult ; Aged ; Antibodies, Monoclonal ; administration & dosage ; adverse effects ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Bone Neoplasms ; drug therapy ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Disease Progression ; Disease-Free Survival ; Drug Administration Schedule ; Female ; Fever ; chemically induced ; Heart Diseases ; chemically induced ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; drug therapy ; metabolism ; Receptor, ErbB-2 ; metabolism ; Soft Tissue Neoplasms ; drug therapy ; secondary ; Trastuzumab