| Objectives: Retrospective investigation on clinical effect of different chemotherapy regimens plus trastuzumab in the treatment of patients suffering from advanced gastric cancer with HER2 positive expression. To investigate the changes of HER2 status and drug resistance gene in patients with advanced HER2 positive gastric cancer before and after treatment with trastuzumab.Methods: 1.The clinical data of 95 patients with HER2-positive advanced gastric cancer treated with trastuzumab combined with chemotherapy in our hospital from March 2007 to September 2016 were collected. Retrospective analysis of trastuzumab combined with different chemotherapy regimens in the first line, second line and cross-line treatment in the efficacy and safety; 2. Tissue specimens of 22 patients were collected before and after treatment from November 2009 to September 2016.The tissue specimens were tested by Immunohistochemistry, Fluorescence in situhybridization and High throughput sequencing to detect transformation of HER2 expression and its related resistance gene.Results: 1 .In the first-line treatment, a total of 74 patients were treated with chemotherapy plus trastuzumab. 38 cases received platinum plus trastuzumab, and 36 cases received paclitaxel plus trastuzumab. The ORR and DCR was 57.9% and 92.1%respectively in the former. In the latter, the ORR and DCR was 55.6% and 94.6%,respectively.The mPFS of the platinum group and the paclitaxel group were 7.3 months and 7.6 months, respectively.The mOS were 26.7 months and 19.2 months, respectively.There was no significant difference between two groups in the short-term efficacy and long-term survival (P> 0.05). 2. Neither reatment-related death nor intolerable adverse reactions occured in the above two groups.The incidence of peripheral neurotoxicity in platinum groupwassignificantly higher than that in the paclitaxel group. However, the incidence of alopecia was significantly higher in the paclitaxel groupthan that in platinum group.3. In the second-line treatment, a total of 48 patients were treated with chemotherapy plus trastuzumab. 27 cases received chemotherapy plus trastuzumab both in the first-line treatment and the second-line treatment, and 21 cases received chemotherapy alone in the second-line treatment. The ORR and DCR was 7.4% and 66.7% respectively in the former.In the latter, the ORR and DCR was 33.3% and 74.1%, respectively. There was significant difference between two groups in the ORR (P=0.022). For the survival, the mPFS and mOS was 3.4 months and 10.9 months respectively in the former.In the latter,the mPFS and mOS was 5.5 months and 15.7 months respectively.There was no significant difference between two groups in mPFS(P=0.088). There was significant difference between two groups in the mOS (P=0.042). 4. In 9 patients without disease progression after receiving chemotherapy plus trastuzumab, the expression of HER2 was significantly decreased after the treatment. Strikingly, the HER2 expression of 2 patients with initial HER2 (+ +) /FISH amplification was negative after treatment. 5. In 8 patients with disease progression after receiving chemotherapy plus trastuzumab, the expression of HER2 of 3 cases was significantly decreased after resistance to the drugs,and 1 patients with initial HER2 positive expression was negative after treatment. In addition, the HER2 expression of two cases was changed form ++ /FISH amplification into wild type. All 8 cases had TP53 gene mutations before and after resistance to the drugs. The PIK3CA gene of 3 cases were changed form wild type into mutations status. One case kept KRAS mutation before and after resistance to the drugs. One case kept ERBB2 mutation before and after resistance to the drugs.One case kept ERBB3 mutation before and after resistance to the drugs.The mTOR expression of one case was amplified before and after drug resistance.Conclusion:The efficacy and long-term survival of trastuzumab plus platinum or paclitaxel in the first-line treatment of patients suffering from advanced gastric cancer with HER2 positive expression have similar therapeutic effect. The ORR of the patients receiving chemotherapy plus trastuzumab both in the first-line treatment and the second-line treatment were significantly higher than those receiving chemotherapy alone in the second-line treatment,mPFS and mOS were prolonged. With or without the resistance to the trastuzumab, the expression of HER2 will be changed. The mutation status of HER2?PIK3CA?KRAS?mTOR?ERBB3 may be related to its primary or acquired resistance to trastuzumab. |
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