No abstract

#407 Introduction:
 The PI3K/Akt/mTOR pathway is often constitutively activated in BC, making inhibition of this pathway an attractive treatment strategy. Temsirolimus (TEM) is an inhibitor of mammalian target of rapamycin (mTOR) inhibitor. A phase II trial of TEM was conducted to determine its activity in MBC and TEM's activity in tumors with PIK3CA mutations.
 Methods:
 An open-label, single-arm, phase II study in patients (pts) with metastatic breast cancer (MBC) was performed at two institutions. TEM (25mg) was intravenously administered weekly. Eligible pts had ECOG performance status (PS) 0 or 1, and albumin > 3.0 mg/dL. Tumor expression of ER, PR, and/or Her2 was required. Prior therapy was not limited. Pts were evaluated for response every 8 weeks of TEM. The primary endpoint was overall response rate, defined as a complete or partial response or stable disease (SD) for ≥ 24 weeks by RECIST. Tumor PIK3CA mutations and immunohistochemical (IHC) expression of PI3K/Akt/mTOR pathway components were evaluated.
 Results:
 Thirty-one pts were enrolled (median age 59; range: 37-80). Pts received a median of 4 prior chemotherapy regimens (range 1-8); pts had ECOG PS 0 (n=14), 1 (n=14), and unknown (n=3). A total of 111 cycles were administered. (median: 2 cycles; range 1-16). Three pts (9.7 %) had prolonged SD for ≥ 24 weeks. Two pts with SD at ≥ 24 weeks had ER+ tumor; all three pts were Her2/neu negative. Seven additional pts had a best response of SD at 16 weeks. One patient achieving SD remains on treatment after 16 cycles.
 The most common adverse events (grades 1-4) include fatigue (n=21), mucositis (n=18), anemia (n=14), increased LFTs (n=14), thrombocytopenia (n=13), rash (n=12), leukopenia (n=12), hypertriglyceridemia (n=11), and hyperglycemia (n=11). Twenty-three pts required a dose reduction or interruption; 3 pts discontinued therapy due to drug toxicity.
 Twenty-three tumors were available for sequencing of PIK3CA helical (HD) and kinase (KD) domains and 24 tumors underwent IHC analysis. Of the three pts with prolonged SD, two pts had tumor with a wildtype PIK3CA sequence in both domains (sequencing on 3rd pt is pending). Four pts had tumor PIK3CA mutations ( 2 pts with HD mutation; 1 with KD; 1 with both HD and KD); these 4 pts had a trend towards decreased progression-free survival versus pts with tumors with wild type PIK3CA (5.3 vs 7.8 weeks). IHC included analysis of pan and phosphorylated: AKT1, S6K1, mTOR, PTEN, and Cyclin D1. Nuclear pAKT308 expression was weakly associated with prolonged PFS (p=0.03).
 Conclusions:
 TEM has limited activity as a single agent in pts with pretreated MBC, and the study did not progress to the planned second stage. Preliminary data suggest that tumors with a mutation in hotspot domains of PIK3CA do not have enhanced sensitivity to TEM.
 This trial was supported by the Avon Foundation and NCI (P30 CA 1459931 S1). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 407.

Background: Xihuang pill has been widely applied as a promising adjunctive drug for gastric cance. However, the exact effects and safety of Xihuang pill have yet to be systematically investigated. We aimed to summarize the effificacy and safety of Xihuang pill for the treatment of advanced GC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials. Methods: The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Relevant randomized controlled trials were searched from PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and echnology Periodical Database, and Chinese Biomedical Literature Database. Papers in English or Chinese published from their inception to October 2020 will be included without any restrictions. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I 2 tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger test. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluate system. Results: The results of our research will be published in a peer-reviewed journal. Conclusion: The conclusion of this study will provide helpful evidence of the effect and safety of Xihuang pill for the treatment of GC in clinical practice. OSF registration number: 10.17605/OSF.IO/VFJAK.

Background: Xihuang pill, a famous traditional Chinese medicine formulation, is a broad-spectrum anti-tumor drug and has been widely used for the treatment of lung cancer in China. The aim of this study is to systematically investigate the efficacy and safety of Xihuang pill for the treatment of lung cancer. Methods: We will perform the comprehensive literature search in the following databases from their inceptions to August 2020 for data extraction: PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I 2 tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger test. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluate system (GRADE) system. Results: The results of our research will be published in a peer-reviewed journal. Conclusion: The conclusion of this study will provide evidence to show whether Xihuang pill is an effective intervention for patient with lung cancer. OSF registration number: 10.17605/OSF.IO/W2GHN

Background: Huaier granules, the aqueous product of Huaier ( Trametes robiniophila Murr. ) extract, are a broad-spectrum anti-tumor drug and have been widely used for the treatment of gastric cancer (GC). The aim of this study is to systematically investigate the efficacy and safety of Huaier granules combined with chemotherapy in the treatment of GC. Methods: Three English databases and four Chinese databases will be searched from its inception to July 2020. Two methodological trained researchers will select the qualified studies for data extraction independently. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.2 and stata 14.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by Cochrane X 2 and I 2 tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger's test. The quality of evidence will be assessed by the GRADE system. Results: The results of our research will be published in a peer-reviewed journal. Conclusion: The conclusion of our systematic review will provide evidence to judge whether Huaier granules combined with chemotherapy is an effective intervention for patient with GC. OSF registration number: 10.17605/OSF.IO/9BVJD.