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Clinical and Experimental Medicine Nov 2023Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2... (Meta-Analysis)
Meta-Analysis Review
Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8-72.7%; 95% CI, 18-32%) and 36.0% (range, 8.3-63.0%; 95% CI, 31-42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16-5.62), 12.78 (95% CI, 10.24-15.32), and 8.12 (95% CI, 6.48-9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade ≥ 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Ado-Trastuzumab Emtansine; Neoplasms; Breast Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37120775
DOI: 10.1007/s10238-023-01072-7 -
Critical Reviews in Oncology/hematology Apr 2023The benefit of adjuvant trastuzumab treatment in patients with HER2-positive breast tumors ≤ 10 mm without lymph node involvement (T1abN0) is insufficiently... (Meta-Analysis)
Meta-Analysis Review
The benefit of adjuvant trastuzumab treatment in patients with HER2-positive breast tumors ≤ 10 mm without lymph node involvement (T1abN0) is insufficiently investigated. The aim of this systematic review and meta-analysis was to examine if adjuvant trastuzumab improves the prognosis in these patients. Databases were searched to identify interventional and observational studies evaluating the effect of trastuzumab on breast cancer specific survival (BCSS), disease free survival (DFS), distant recurrence free survival (DRFS), overall survival (OS) or recurrence free survival (RFS). Twelve studies examining the effect of trastuzumab and nine control studies without trastuzumab were identified (n = 6927). Median follow-up was 36-123 months. Significantly improved DFS (Hazard Ratio (HR) 0.14, p < 0.0001) and OS (HR 0.17, p = 0.011) were found for patients receiving trastuzumab and chemotherapy compared to no trastuzumab/chemotherapy based on four and two studies. The prognosis was good even for patients without trastuzumab treatment: 5-year DFS 88.3% and 5-year OS 95.9%.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Breast Neoplasms; Prognosis; Disease-Free Survival; Adjuvants, Immunologic; Chemotherapy, Adjuvant
PubMed: 36854373
DOI: 10.1016/j.critrevonc.2023.103952 -
Pharmaceuticals (Basel, Switzerland) Jul 2023There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation.... (Review)
Review
There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation. Recently, randomized controlled trials (RCTs) have evaluated the effects of early commitment of beta-blockers (BBs), angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) during trastuzumab chemotherapy in order to prevent the related cardiotoxicity. The present systematic review and meta-analysis of six RCTs included patients who have predominantly non-metastatic, HER2-positive, breast cancer and received trastuzumab as primary or adjuvant therapy. Those patients did not have any obvious cardiac dysfunction or any previous therapy with cardioprotective agent. We evaluated the efficacy of the aforementioned medications for primary prevention of cardiotoxicity, using random effects models. Any preventive treatment did not reduce cardiotoxicity occurrence compared to controls (Odds ratios (OR) = 0.92, 95% CI 0.54-1.56, = 0.75). Results were similar for ACEIs/ARBs and beta-blockers. Treatment with ACEIs/ARBs led to a slight, but significant, increase in LVEF in patients compared to the placebo group. Only two studies reported less likelihood of discontinuation of trastuzumab treatment. More adequately powered RCTs are needed to determine the efficacy of routine prophylactic therapy.
PubMed: 37513895
DOI: 10.3390/ph16070983 -
Frontiers in Oncology 2023Many options for third-line treatment of advanced gastric cancer (GC) or gastroesophageal junction carcinoma (GEJC) have been developed. Therapies including...
BACKGROUND
Many options for third-line treatment of advanced gastric cancer (GC) or gastroesophageal junction carcinoma (GEJC) have been developed. Therapies including immunotherapy (nivolumab), chemotherapy (irinotecan, FTD/TPI), targeted therapy (apatinib), and antibody drug conjugates (ADC) have shown to increase the survival rates in patients, but few studies have compared the relative efficacy of these treatments. Here, we compared the efficacies of these regimens using network meta-analysis (NMA) to provide guides in selecting the best regimen and formulating a precise individualized treatment plan.
METHODS
The published RCTs of phase II/III in PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched. The median overall survival (mOS) was the primary outcome of NMA, and the other outcomes were median progression-free survival (mPFS), disease control rate (DCR) (proportion of patients with confirmed CR, PR, or stable disease (SD)) and incidence of grade 3 or above adverse events (≥3AEs).
RESULTS
Five phase II/III RCTs involving 1674 patients and 7 treatment regimens were analyzed. It showed that Trastuzumab Deruxtecan (DS-8201) prolonged the OS of patients significantly comparing with chemotherapy (HR: 0.59; 95% CI: 0.39-0.89) for the overall population. DS-8201 (HR: 0.27; 95% CI: 0.17-0.42) and chemotherapy (HR: 0.57; 95% CI: 0.47-0.7) improved the PFS significantly over nivolumab. Apatinib (RR: 3.04; 95% CI: 1.65-5.95) and DS-8201 (RR: 2.67; 95% CI: 1.51-4.83) were more effective than nivolumab in improving DCR. DS-8201 achieved greater OS benefits compared to chemotherapy (HR: 0.59; 95% CI: 0.39-0.88) for patients who were HER2-positive. We ranked the Bayesian surface under the cumulative ranking curve according to OS benefit, and showed that ADC ranked first for the general patient population and for patients with a HER2-positive diagnosis, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. For patients with GEJC, nivolumab ranked first.
CONCLUSIONS
Nivolumab, apatinib, chemotherapy, and ADC all improved the OS of GC/GEJC patients significantly. ADC may be the best option for the overall population of GC, as well as for patients with HER2-overexpression, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. Nivolumab may be the first treatment option for GEJC patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022364714.
PubMed: 36937403
DOI: 10.3389/fonc.2023.1118820 -
Biochimica Et Biophysica Acta. Reviews... Jan 2023This systematic review and meta-analysis study investigates the predictive and prognostic value of PIK3CA mutations for HER2-positive breast cancer treated with tyrosine... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis study investigates the predictive and prognostic value of PIK3CA mutations for HER2-positive breast cancer treated with tyrosine kinase inhibitors (TKIs). A search of the Medline, Embase, and Cochrane Library databases yielded 17 eligible studies (1706 patients). In 10 neoadjuvant studies, the pathological complete response rate was significantly higher in wild-type PIK3CA (WT) patients than in mutated PIK3CA (MT) patients (OR = 0.45; 95% CI = 0.31-0.65; P < 0.001). In five metastasis studies, the pooled objective response rate was significantly higher in WT patients than in MT patients (OR = 0.40; 95% CI = 0.23-0.70; P = 0.001). Four metastasis studies indicated that PIK3CA mutations had a marginally significant relationship with poor progression-free survival and overall survival. Thus, PIK3CA mutations have predictive value for the treatment response of early/advanced-stage HER2-positive breast cancer treated with TKI-containing regimens.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Tyrosine Kinase Inhibitors; Receptor, ErbB-2; Prognosis; Neoadjuvant Therapy; Class I Phosphatidylinositol 3-Kinases
PubMed: 36516931
DOI: 10.1016/j.bbcan.2022.188847 -
Expert Review of Clinical Pharmacology Nov 2022Interstitial lung disease (ILD) events associated with anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) have aroused wide attention. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Interstitial lung disease (ILD) events associated with anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) have aroused wide attention.
RESEARCH DESIGN AND METHODS
In meta-analysis, we systematically reviewed literatures, and the outcomes were the proportion and risk of ILD related to anti-HER2 ADCs. A disproportionality analysis based on data from VigiBase was conducted to characterize the main features of anti-HER2 ADC-related ILD/pneumonitis.
RESULTS
Two hundred and forty-five all-grade and 47 grade ≥ 3 ILD events with the proportion of 4.4% (95% confidence interval (CI) [2.0%, 6.8%]) and 0.5% (95% CI [0.3%, 0.8%]) were observed for anti-HER2 ADCs, respectively. Trastuzumab emtansine, trastuzumab deruxtecan and trastuzumab duocarmazine significantly increased the risk of all-grade and grade ≥ 3 ILD events with Peto odd ratios of 2.62 (95% CI [1.71, 4.04], P < 0.0001) and 2.82 (95% CI [1.07, 7.42], P = 0.04), respectively. In VigiBase, 271 cases of ILD/pneumonitis related to trastuzumab emtansine and trastuzumab deruxtecan were extracted. The median time to the onset of event was 86 days and 54.95% of events occurred within 3 months.
CONCLUSIONS
Trastuzumab emtansine, trastuzumab deruxtecan and trastuzumab duocarmazine increased the risk of ILD, which can lead to serious outcomes and tends to occur early.
Topics: Humans; Female; Ado-Trastuzumab Emtansine; Pharmacovigilance; Trastuzumab; Receptor, ErbB-2; Immunoconjugates; Antineoplastic Agents; Lung Diseases, Interstitial; World Health Organization; Breast Neoplasms
PubMed: 36111954
DOI: 10.1080/17512433.2022.2121705 -
ESMO Open Feb 2024Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the human epidermal growth factor receptor 2 (HER2)-positive BCBM population.
PATIENTS AND METHODS
We searched PubMed, Embase, and Cochrane Library databases as well as American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and San Antonio Breast Cancer Symposium (SABCS) websites for clinical trials (CTs) and observational studies evaluating T-DXd in patients with HER2-positive BCBM. Heterogeneity was assessed with I statistics. Random effects models were used for all statistical analyses, which were carried out using R software (version 4.2.2).
RESULTS
Ten studies were included, six CTs (n = 189) and four observational studies (n = 130), with a total of 319 patients. The median progression-free survival was 15 months [95% confidence interval (CI) 13.9-16.1 months]. The objective response rate (ORR) was 61% (95% CI 52% to 70%), and the intracranial (IC)-ORR was 61% (95% CI 54% to 69%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (P = 0.31 and 0.58, respectively). The clinical benefit rate (CBR) was 80% (95% CI 52% to 94%), and the IC-CBR was 70% (95% CI 54% to 82%). The ORR was 68% (95% CI 57% to 77%) in the subgroup of patients with stable BMs and 60% (95% CI 48%-72%) in patients with active BM, with no significant difference between groups (P = 0.35).
CONCLUSIONS
Our systematic review and meta-analysis supports the IC activity of T-DXd in patients with stable BM and active BM.
TRIAL REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023422589.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Brain Neoplasms; Camptothecin; Receptor, ErbB-2; Immunoconjugates
PubMed: 38320430
DOI: 10.1016/j.esmoop.2024.102233 -
BMC Women's Health Apr 2021Trastuzumab is currently the standard treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, it is not recommended for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab is currently the standard treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, it is not recommended for HER2-positive breast cancer patients during pregnancy as it may jeopardize safety of the fetus. Nevertheless, there is evidence that fetuses exposed to trastuzumab in early stages of pregnancy remain healthy METHODS: To evaluate the possible effects of trastuzumab on fetus and provide evidence on the safety of trastuzumab in early pregnancy in HER2-positive breast cancer patients, we analyzed 22 studies involving 22 pregnant women and 23 fetuses.
RESULTS
Based on the meta-analysis, the gestational week of exposure to trastuzumab is 0-34 weeks, the average duration of use is 17 weeks, and the average gestational week of delivery is 34.3 weeks. Complications occurred in 77.27% of patients during pregnancy and 56.52% of newborns。The main complication during pregnancy was anhydramnios (68.18%), while the main complications at birth were Respiratory distress or tachypnea (30%). After an average of 25.28 months of follow-up, 17.39% (4/23) of the children died. There was no complication during pregnancy or at birth in patients treated with trastuzumab during early pregnancy (P = 0.043). Patients older than 30 who received trastuzumab during pregnancy were more likely to have neonatal complications (OR = 7.778, 95%CI = 1.2-50.424, P = 0.04).
CONCLUSION
These results suggest that trastuzumab use during pregnancy can cause pregnancy,fetal and newborn complications. However, exposed to trastuzumab only in the first trimester are less likely to have pregnancy and fetal complications. Patients with gestational age below 30 years are less likely to have neonatal complications after trastuzumab during pregnancy. Terminating pregnancy should not be the only option for such patients. But more evidence is needed to verify this conclusion.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Child; Female; Gestational Age; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Neoplastic; Receptor, ErbB-2; Trastuzumab
PubMed: 33882925
DOI: 10.1186/s12905-021-01301-9 -
Systematic Reviews Dec 2022Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from lapatinib and lapatinib plus trastuzumab therapy than standard trastuzumab therapy. This study presents an update of a systematic review and meta-analysis involving comparison of lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy.
AIM
We determined whether trastuzumab plus lapatinib or lapatinib therapy is not inferior to trastuzumab therapy in HER2-positive breast cancer patients.
METHODS
Relevant trials were searched in CNKI, Wanfang, VIP, Sinomed, PubMed, Embase, and Cochrane CENTRAL databases from inception until October 25, 2021. Primary outcomes were OS, DFS/EFS, and PFS while secondary outcomes were pCR (ypT0/is ypN0), pCR (ypT0/is ypN0/+), ORR, DCR, rate of BCS, RFS, cardiac toxicities, and other toxicities.
RESULTS
Thirteen randomized controlled trials were included in this study. Trastuzumab combined with lapatinib therapy was found to be superior to standard trastuzumab therapy alone with regard to overall survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0), pathologic complete response (ypT0/is ypN0/+), recurrence-free survival, higher incidences of diarrhea, and rash/skin toxicity. Lapatinib therapy was established to be inferior to trastuzumab therapy in overall survival, progression-free survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0) and pathologic complete response (ypT0/is ypN0/+), diarrhea, and rash/skin toxicity and had a low incidence of left ventricular ejection fraction decline.
CONCLUSIONS
The efficacy of trastuzumab combined with lapatinib therapy is superior to standard trastuzumab therapy alone; however, it has more non-cardiac grade III/IV toxicities. Moreover, the efficacy of lapatinib therapy is inferior to that of standard trastuzumab therapy alone.
Topics: Humans; Female; Trastuzumab; Lapatinib; Breast Neoplasms; Receptor, ErbB-2; Stroke Volume; Antineoplastic Combined Chemotherapy Protocols; Ventricular Function, Left; Randomized Controlled Trials as Topic
PubMed: 36496473
DOI: 10.1186/s13643-022-02134-9 -
Breast Cancer Research and Treatment Dec 2021Docetaxel, carboplatin and trastuzumab, with or without pertuzumab (TCH(P)), has become the preferred (neo)adjuvant regimen for HER2-positive breast cancer. However, its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Docetaxel, carboplatin and trastuzumab, with or without pertuzumab (TCH(P)), has become the preferred (neo)adjuvant regimen for HER2-positive breast cancer. However, its associated febrile neutropenia (FN) risk is unclear: pivotal studies reported FN risks < 10%, but in clinical practice, a high FN rate (> 20%) was observed. This systematic review and meta-analysis determine the FN risk associated with TCH(P) and the indication for primary prophylactic granulocyte colony-stimulating factor (PP G-CSF).
METHODS
The MEDLINE, Embase, Web of Science and Cochrane databases were searched for full-text English articles reporting the FN incidence in early breast cancer patients receiving (neo)adjuvant TCH(P). The primary endpoint was the pooled crude FN incidence in patients treated without PP G-CSF using the random effects method. Secondary endpoints were the FN risk with PP G-CSF support, age-related differences in FN and differences in risk with TCH versus TCHP.
RESULTS
Seventeen studies were included in the systematic review. The pooled estimates of FN incidences were 27.6% (95% CI 18.6 to 37.1) in patients who did not receive PP G-CSF (primary meta-analysis, 9 studies, n = 889) versus 5.0% (95% CI 2.6 to 8.0) in patients administered PP G-CSF (secondary meta-analysis, 7 studies, n = 445). Two studies reported non-significant age-related differences in FN. The risk comparison between TCH and TCHP was inconclusive.
CONCLUSIONS
The crude FN risk associated with (neo)adjuvant TCH(P) is over 20%, the upper limit above which the international guidelines unanimously advise PP G-CSF administration. G-CSF prophylaxis effectively reduces FN risk and should become the standard of care with (neo)adjuvant TCH(P).
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Docetaxel; Febrile Neutropenia; Female; Granulocyte Colony-Stimulating Factor; Humans
PubMed: 34533681
DOI: 10.1007/s10549-021-06387-1