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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. [ABSTRACT FROM AUTHOR]

Although platinum-based chemotherapy can improve pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC), the impact on survival of platinum-based neoadjuvant and adjuvant chemotherapy is still controversial. Our meta-analysis aimed at analyzing survival with platinum-based neoadjuvant and adjuvant chemotherapy in patients with TNBC. We searched PubMed, EMBASE, MEDLINE, Cochrane databases, and several major conferences up to January 2021. Fixed and random models were used for our meta-analysis. Disease-free survival (DFS), overall survival (OS), and side effects data were extracted from the included literature in addition to the corresponding pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). A total of nine studies involving 3247 patients were included. The pooled analysis suggested that compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy could further improve DFS (HR = 0.56, 95% CI 0.45–0.67, p < 0.01) and OS (HR = 0.54, 95% CI 0.38–0.70, p < 0.01) in patients with TNBC. The subgroup analysis showed that platinum-based chemotherapy could further improve DFS (HR = 0.59, 95% CI 0.43–0.74, p < 0.01) and OS (HR = 0.61, 95% CI 0.40–0.83, p < 0.01) in neoadjuvant chemotherapy and DFS (HR = 0.53, 95% CI 0.37–0.69, p < 0.01) and OS (HR = 0.46, 95% CI 0.23–0.69, p < 0.01) in adjuvant chemotherapy compared with anthracycline- and/or paclitaxel-based chemotherapy in patients with TNBC. In addition, compared with anthracycline-based chemotherapy, platinum-based chemotherapy without anthracycline chemotherapy could further improve DFS (HR = 0.53, 95% CI 0.37–0.70, p < 0.01) and OS (HR = 0.46, 95%CI 0.19–0.72, p < 0.01) in patients with TNBC. Compared with anthracycline- and/or paclitaxel-based chemotherapy, all-grade diarrhea, fatigue, and grade ≥ 3 anemia were higher in platinum-based chemotherapy. In contrast, all-grade anemia, leukopenia, neutropenia, peripheral neuropathy, myalgia/arthralgia, cardiac toxicity were lower in platinum-based chemotherapy; grade ≥ 3 leukopenia, neutropenia and myalgia/arthralgia were also lower. Compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy was more associated with improved DFS and OS in TNBC patients. The benefit of survival is consistent with platinum-based neoadjuvant and adjuvant chemotherapy. The side effects of platinum-based chemotherapy are tolerable. [ABSTRACT FROM AUTHOR]

The Watson for Oncology (WFO) decision system has been rolled out in many cancers. However, the consistency of treatment for breast cancer is still unclear in relatively economically disadvantaged areas. Patients with postoperative adjuvant stage (January 2017 to December 2017) and advanced-stage breast cancer (January 2014 to December 2018) in northwest of China were included in this study. Patient information was imported to make treatment decisions using Watson version 19.20 analysis and subsequently compared with clinician decisions and analyzed for influencing factors. A total of 263 patients with postoperative adjuvant breast cancer and 200 with advanced breast cancer were included in this study. The overall treatment modality for WFO was in 80.2% and 50.5% agreement with clinicians in the adjuvant and advanced-stage population, respectively. In adjuvant treatment after breast cancer surgery, menopausal status (odds ratio (OR) = 2.89, P = 0.012, 95% CI, 1.260–6.630), histological grade (OR = 0.22, P = 0.019, 95% CI, 0.061–0.781) and tumor stage (OR = 0.22, P = 0.042, 95% CI, 0.050–0.943) were independent factors affecting the concordance between the two stages. In the first-line treatment of advanced breast cancer, hormone receptor status was a factor influencing the consistency of treatment (χ2 = 14.728, P < 0.001). There was good agreement between the WFOs and clinicians' treatment decisions in postoperative adjuvant breast cancer, but poor agreement was observed in patients with advanced breast cancer. [ABSTRACT FROM AUTHOR]

Neoadjuvant treatment options for triple-negative breast cancer (TNBC) are abundant, but the efficacy of different combinations of treatment options remains unclear. Our network meta-analysis aimed to evaluate the effectiveness and safety of various neoadjuvant treatment options in patients with TNBC. Literature reports published before March 31, 2022, were retrieved from the PubMed, Embase, Cochrane Library, main oncology conference of the European Society of Medical Oncology, American Society of Clinical Oncology, and San Antonio Breast Cancer Symposium databases. Pairwise and Bayesian network meta-analyses were performed to compare direct and indirect evidence, respectively. The primary outcome was pathological complete response (pCR). Comparison of efficiency between different treatment regimens was made by HRs and 95% confidence intervals (CIs). Overall, 26 studies, including 9714 TNBC patients, were assessed in this network meta-analysis. Results indicated that the pCR of immune checkpoint inhibitors plus platinum-containing regimens is better than other joint regimens. PCR rate of neoadjuvant chemotherapy regimens containing bevacizumab, platinum, poly(ADP-ribose) polymerase inhibitors, and immune checkpoint inhibitors was higher than those of standard chemotherapy agents. By performing a conjoint analysis of the pCR rate and safety endpoints, we found that immune checkpoint inhibitors plus platinum-containing regimens were well balanced in terms of efficacy and toxicity. Considering the efficacy and acceptable adverse events, neoadjuvant chemotherapy based on immune checkpoint inhibitors plus platinum may be considered as an option for patients with TNBC. [ABSTRACT FROM AUTHOR]

The combination of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and endocrine treatment has benefited patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer; however, its effects in the neoadjuvant setting for ER + /HER2- early breast cancer (EBC) are unclear. Systematic searches were performed in PubMed, Embase, Cochrane Library, and major oncological meetings for trials of CDK4/6 inhibitors plus neoadjuvant endocrine treatment (NET) vs. NET/neoadjuvant chemotherapy (NACT) alone up to January 30, 2021. We assessed the efficacy of CDK4/6 inhibitors plus NET vs. NET/NACT alone in ER + /HER2- EBC. Six studies that included 803 patients treated with CDK4/6 inhibitors plus NET vs. NET/NACT alone were used. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased the complete cell cycle arrest (CCCA) rate (OR, 9.00; 95% CI, 5.42–14.96; P < 0.001). Nonsignificant differences between CDK4/6 inhibitors and NET/NACT alone occurred in the preoperative endocrine prognostic index (PEPI)-0 rate (OR, 1.13; 95% CI, 0.59–2.18; P = 0.71), pathological complete response (pCR) rate (OR, 0.75; 95% CI, 0.13–4.29; P = 0.74), objective response rate (ORR) (OR, 0.70; 95% CI, 0.21–2.29; P = 0.55), and disease control rate (DCR) (OR, 1.16; 95% CI, 0.47–2.89; P = 0.74). CDK4/6 inhibitors plus NET indicated a high risk of neutropenia (OR, 56.43; 95% CI, 15.76–202.11; P < 0.001) as an adverse effect (AE) and elevated alanine aminotransferase (ALT) level (OR, 15.30; 95% CI, 2.02–115.98; P = 0.008) as grade 3/4 AEs. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased CCCA rate in ER + /HER2- EBC patients. CDK4/6 inhibitors plus NET did not substantially improve the PEPI-0 rate, pCR rate, ORR, or DCR. The combination increased the risk of neutropenia and elevated ALT levels. In the neoadjuvant setting, addition of CDK4/6 inhibitors to NET may be an option for treating ER + /HER2- EBC. [ABSTRACT FROM AUTHOR]