scholarly journals R0 resection of Stage IV HER2-positive gastric cancer after the first-line chemotherapy: a case of successful conversion therapy

2017 ◽  
Vol 25 (2) ◽  
pp. 60-62
Author(s):  
Yuki Fujieda ◽  
Hiromichi Maeda ◽  
Toyokazu Akimori ◽  
Norihito Kamioka ◽  
Tsutomu Namikawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stage Iv ◽  
R0 Resection ◽  
Conversion Therapy ◽  
First Line ◽  
Her2 Positive ◽  
Line Chemotherapy

scholarly journals Prognostic benefit of conversion surgery for HER2 positive stage IV gastric cancer; a case series study of eleven patients treated with trastuzumab-based chemotherapy

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Koichi Hayano ◽  
Hiroki Watanabe ◽  
Takahiro Ryuzaki ◽  
Naoto Sawada ◽  
Gaku Ohira ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Stage Iv ◽  
R0 Resection ◽  
Conversion Surgery ◽  
First Line ◽  
Her2 Positive ◽  
Stage Iv Gastric Cancer ◽  
Gastric Cancer Patients ◽  
First Line Treatment

Abstract Background Since the ToGA trial, trastuzumab-based chemotherapy is the standard treatment for HER2 positive stage IV gastric cancer. However, it is not yet clear whether surgical resection after trastuzumab-based chemotherapy (conversion surgery) can improve survival of HER2 positive stage IV gastric cancer. The purpose of this study is to evaluate the prognostic benefit of conversion surgery in HER2 positive stage IV gastric cancer patients. Case presentation We retrospectively investigated the medical records of the patients with HER2 positive (IHC3(+) or IHC2(+)/FISH(+)) stage IV gastric cancer treated with trastuzumab-based chemotherapy as the first line treatment. Overall survival (OS) was compared between patients with conversion surgery and without. Eleven HER2 positive stage IV gastric cancer patients treated with trastuzumab-based chemotherapy as the first line treatment were evaluated. Response rate was 63.6%, and 6 of 11 patients could receive conversion surgery. R0 resection was achieved in four patients. In Kaplan–Meier analysis, patients who received conversion surgery showed significantly better OS than those without surgery (3-year survival rate, 66.7% vs. 20%, P = 0.03). The median OS of patients who achieved R0 resection is 51.8 months. Conclusions Conversion surgery might have a survival benefit for HER2 positive stage IV gastric cancer patients. If curative surgery is technically possible, conversion surgery could be a treatment option for HER2 positive stage IV gastric cancer.

Survival of patients with HER2-positive gastric cancer with introduction of trastuzumab.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 128-128
Author(s):  
Kohei Shitara ◽  
Yasushi Yatabe ◽  
Masato Sugano ◽  
Keitaro Matsuo ◽  
Chihiro Kondo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Small Sample Size ◽  
Small Sample ◽  
Her2 Status ◽  
First Line ◽  
Her2 Positive ◽  
Line Therapy ◽  
The Impact ◽  
Time Varying Covariates ◽  
Line Chemotherapy

128 Background: ToGA study showed that trastuzumab given in combination with first-line chemotherapy (fluoropyrimidine plus cisplatin) improved the overall survival of HER2-positive patients with advanced gastric cancer (AGC). Meanwhile, the prognostic value of HER2 or the efficacy of trastuzumab in second- or further-line chemotherapy remains controversial. Methods: We retrospectively analyzed 567 patients with AGC who initiated systemic chemotherapy before March 2011. Among them, 287 were evaluated for their HER2 status. HER2 positivity was defined as IHC 3+ or IHC 2+ with amplification by FISH. Treatment outcomes were compared between patients with HER2-positive and HER2-negative AGC. To evaluate the impact of exposure to trastuzumab in any line of chemotherapy, we applied time-varying covariates (TVC) analysis to avoid possible lead-time bias. Results: The median survival time (MST) of HER2-evaluated patients (n=287) tended to be better than that of HER2-non-evaluated patients (n=280, 14.5 vs. 13.2 months; P=0.03). Among the HER2-evaluated patients, 47 (16.3%) were HER2-positive and had longer survival than HER2-negative patients (24.1 vs. 13.4 months; P=0.05). Among the HER2-positive patients, 35 received trastuzumab; 15 patients received it as first-line therapy and 20 received it as second- or further-line therapy. The MST of HER2-positive patients with trastuzumab treatment was significantly longer than that of HER2-positive patients without trastuzumab (26.6 vs. 13.5 months; P=0.015). HER2-negative patients and HER2-positive patients without trastuzumab had similar survival durations. According to multivariate analysis with TVCs, exposure to trastuzumab was independently associated with better prognosis (HR 0.54, P=0.04). Conclusions: Although the retrospective nature and small sample size are major limitations of this study, recent HER2-positive AGC patients showed a better prognosis than HER2-negative patients, especially with the introduction of trastuzumab.

Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: A multicenter AGEO study.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 94-94 ◽  
Author(s):  
Juliette Palle ◽  
David Tougeron ◽  
Astrid Pozet ◽  
Emilie Soularue ◽  
Pascal Artru ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Univariate Analysis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Her2 Positive ◽  
Second Line Chemotherapy ◽  
Platinum Based Chemotherapy ◽  
Line Chemotherapy

94 Background: Trastuzumab in combination with platinum-based chemotherapy is the standard first line regimen in HER2 positive advanced gastric cancer. However, there is no data concerning continuation of trastuzumab beyond first line progression. Methods: This retrospective multicenter study include all consecutive patients with HER2 + advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received after progression of trastuzumab plus platinum-based chemotherapy, a second line chemotherapy with irinotecan, taxane or platinum salt, with or without trastuzumab. The prognostic variables with P values ≤0.10 in univariate analysis were eligible for the Cox multivariable regression model. Results: From August 2007 to March 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; PS 0-1, 71.2%) with advanced (metastatic : 99%) gastric (45.2%) or GEJ (54.8%) cancer. All patients had received first line treatment based on trastuzumab plus fluoropyrimidine and cisplatin (n=54; 51.9%) or oxaliplatin (n=50; 48.1%). As second line chemotherapy, 67 patients (64.4%) received FOLFIRI regimen, including 19 who have continued trastuzumab; 23 patients (22.1%) received a taxane regimen (paclitaxel or docetaxel), including 12 with trastuzumab; and 14 patients (13.5%) received a platinum-based chemotherapy (different from that used in first-line), including 8 with trastuzumab. When considering all regimens of second-line chemotherapy, continuation (n=39) versus discontinuation (n=65) of trastuzumab was significantly associated with an increase on PFS (4.4 vs 2.3 months; p=0.002) and OS (12.6 vs 6.1 months; p=0.001). In multivariate Cox model (including ECOG PS, tumor grade, number of metastatic site, and second-line treatment), continuation of trastuzumab was significantly associated with longer PFS (HR=0.56; 95%CI [0.35-0.89]; p=0.01) and OS (HR=0.47; 95%CI [0.28-0.79]; p=0.004). Conclusions: This study suggests that maintenance of trastuzumab plus second line chemotherapy beyond disease progression has clinical benefit in patients with HER2 positive advanced gastric cancer. These results deserve a prospective randomized validation.

CO-STAR: Surgical conversion feasibility trial of sintilimab (PD-1 inhibitor) combined with Nab-PTX, S-1 and apatinib for the first-line treatment of stage IV gastric cancer (GC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16041-e16041
Author(s):  
Qiang Xue ◽  
Baogui Wang ◽  
Xiaona Wang ◽  
Xuewei Ding ◽  
Yong Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Conversion Rate ◽  
Tumor Response ◽  
Stage Iv ◽  
R0 Resection ◽  
Line Treatment ◽  
First Line ◽  
Stage Iv Gastric Cancer ◽  
Peritoneal Spread ◽  
First Line Treatment

e16041 Background: Chemotherapy and PD-1 inhibitor have shown significant clinical benefits in first-line treatment of GC, overall survival was still dismal. The surgical intervention with curative or life prolonging intention was evaluated as feasible for stage IV GC from clinical trials and retrospective cohorts. Our previous study of cytotoxic chemotherapy (S-1 & PTX) in combination with multi-targets anti-angiogenic TKIs illustrated increased response and R0 resection rate. Given the enhanced response from chemo, PD-1 and TKIs regimens, this trial was designed to assess the feasibility of surgical conversion from this combination in stage IV GC. Methods: This is a prospective, single-arm, single-center, phase II trial. Eligible criteria were treatment naïve, histopathologically confirmed stage IV (AJCC8th) and ECOG PS 0-1 GC adenocarcinoma. Pts were given with sintilimab (200mg, iv, d1) combined with Nab-PTX (w/o peritoneal spread: 260 mg/m2, iv, d1; w/ peritoneal spread: 180 mg/m2, iv, d1 and 80 mg/m2, ip, d1), S-1 (60mg, po, bid, d1-14), and apatinib (250mg, po, qd) every 3 wks. Tumor response was assessed every 2-4 cycles by radiologic imaging and MDT was employed to determine surgical feasibility. Safety run-in was employed in the first 3+3 pts by DLTs to determine the tolerability. The primary endpoint was ORR and R0 surgical conversion rate. Results: 42 pts were enrolled up to 2/2021. The median follow-up was 3.5m (range 0.7-11.3). The median age was 56 yrs (range 31-72), male was 47.6%, and PS 1 was 31.0%. The metastatic factors were characterized as No.16 lymph nodes 54.8% (23), liver 23.8% (10), peritoneum 40.5% (17), Krukenberg 2.4% (1), and extensive metastases (≥2 organs) 42.9% (18). No DLT occurred in initial 6 pts. Of 36 evaluable pts, ORR was 61.1% and DCR was 97.2%. Surgical conversion was currently identified in 18 pts with 94.4% (17) R0 resection, and the R0 surgical conversion rate was 47.2% (17/36). Median treatment cycle in converted pts was 4. 22.2% (4/18) pts achieved pathological complete response (TRG 0), and 27.8% (5/18) pts had major response (TRG 0-1). The most common AEs were grade 1-2, and 1 SAE of hemorrhage grade 4 occurred. No increase of anastomotic leakage, hemorrhage, and abdominal infection, and no surgery caused death and complication caused second operation occurred. The median postoperative length of stay was 9.5d (range 6-16). Conclusions: These preliminary results showed favorable tumor response and acceptable tolerability for potential surgical resection. Sintilimab, doublet chemotherapy, and apatinib might offer an opportunity of cure for stage IV gastric cancer. Trial ID: NCT04267549. Clinical trial information: NCT04267549. [Table: see text]

scholarly journals Results of the use of trastuzumab combined with different chemotherapy regimens in first-line treatment of HER2-positive disseminated gastric cancer

2019 ◽  
pp. 120-127
Author(s):  
N. S. Besova ◽  
T. A. Titova ◽  
S. G. Bagrova ◽  
E. S. Obarevich ◽  
V. A. Gorbunova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Objective Response ◽  
Stage Iv ◽  
Tumour Regression ◽  
First Line ◽  
Her2 Positive ◽  
Mortality Pattern ◽  
Stage Iv Gastric Cancer ◽  
Triplet Chemotherapy ◽  
Doublet Chemotherapy

Gastric cancer (GC) is one of the most common types of malignant tumour worldwide and is ranked fifth in the cancer incidence pattern and third in the cancer mortality pattern. In the Russian Federation, 39.9% of patients are diagnosed with stage IV gastric cancer, 46.6% of patients die within the first year after diagnosis. The combinations of trastuzumab with platinum derivatives and fluoropyrimidines (trastuzumab + doublet) are regarded as the standard therapy against HER2 positive disseminated gastric cancer. We studied the efficacy and toxicity of the combination of trastuzumab with three-component (triple) chemotherapy regimens (docetaxel or irinotecan + platinum derivatives and fluoropyrimidines). In combination of trastuzumab with triplet chemotherapy, an objective response was achieved in 76.7% of cases, with doublet chemotherapy it was achieved in 60% (p = 0.228), of which complete tumour regression was observed in 10%, control of the disease was reported in 96.7% and 95.0 % (p = 1.0) patients, respectively. The median progression-free survival in patients, who received trastuzumab in combination with triplet chemotherapy, was 9.66 months, in combination with doublet chemotherapy was 11.07 months, the difference was not statistically significant (p = 0.800; OR = 0.908; 95% CI: 0.430–1.918). Median survival of patients is not achieved. The obtained results showed that adding a third cytostatic agent to the standard duplet chemotherapy in combination with trastuzumab does not lead to improvement in the treatment outcomes of first-line therapy in patients with HER2-positive disseminated gastric cancer.

Depth of response predicts the clinical outcome of advanced HER2-positive gastric cancer to trastuzumab-based first-line chemotherapy

2017 ◽  
Vol 80 (4) ◽  
pp. 807-813 ◽  
Author(s):  
Shigenori Kadowaki ◽  
Toshiki Masuishi ◽  
Tetsuya Eto ◽  
Yukiya Narita ◽  
Hiroya Taniguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Outcome ◽  
First Line ◽  
Her2 Positive ◽  
Depth Of Response ◽  
Line Chemotherapy

Phase II study of trastuzumab in combination with capecitabine and oxaliplatin in patients with advanced gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 83-83 ◽  
Author(s):  
Min-Hee Ryu ◽  
Baek-Yeol Ryoo ◽  
Young Soo Park ◽  
Sook Ryun Park ◽  
Jong Gwang Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Drop Out ◽  
First Line ◽  
Her2 Positive ◽  
Ecog Performance Status ◽  
Line Chemotherapy

83 Background: Trastuzumab (Herceptin) in combination with capecitabine and cisplatin has been the standard first-line chemotherapy in patients with HER2-positive advanced gastric cancer (AGC). Oxaliplatin is generally less toxic and more convenient than cisplatin, and currently replacing cisplatin for the treatment of AGC. This study aims to investigate the efficacy and safety of trastuzumab in combination with capecitabine and oxaliplatin (HER-XELOX) in HER2-positive AGC. Methods: With Simon’s minimax two stage design (P0[response rate of historic control]=0.4, P1=0.55, two-sided alpha=0.1, beta=0.2, and 10% drop-out rate), a total of 55 patients with AGC positive for HER2 defined as either HER2 immunohistochemistry (IHC) 3+ or IHC 2+and FISH+ were enrolled from Aug 2011 to Feb 2013. HER-XELOX regimen consisted of trastuzumab 8 mg/kg i.v. on day 1 in cycle 1 and then 6 mg/kg in subsequent cycles, capectabine 2000 mg/m2/day p.o. on days 1-14, and oxaliplatin 130 mg/m2i.v. on day 1, every 3 weeks. HER-XELOX was administered as a first-line chemotherapy until disease progression, unacceptable toxicity, or consent withdrawal. Results: Among the 55 patients, 37 (66%) patients were male. Median age was 57 years (range, 29-74). ECOG performance status was 0-1 in 51 (93%) patients. Fifty three (96.4%) patients had metastatic disease, and 2 (3.6%) had locally advanced unresectable disease. With complete response in 2 patients and partial response in 35 patients, confirmed overall response rate was 67.3% (95% CI, 54-80%). With a median follow-up of 13.8 months (range, 6.1-23.9) in surviving patients, median progression-free survival was 9.8 months (95% CI, 7.0-12.6). Median overall survival was 21.0 months (95% CI, 6.4-35.7). Common grade 3 or 4 toxicities with frequency > 10% included neutropenia (18.2%), anemia (10.9%), and neuropathy (10.9%). There was no febrile neutropenia. One patient died of treatment-related diarrhea and sepsis. Conclusions: HER-XELOX regimen is well tolerated and highly effective in patients with HER2-positive AGC. Clinical trial information: NCT01396707.

Survival impact of the response at twelve weeks in patients with advanced gastric cancer received first-line chemotherapy.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 103-103
Author(s):  
Motoko Arakaki ◽  
Masahiko Aoki ◽  
Hiroshi Imazeki ◽  
Hirokazu Shoji ◽  
Yoshitaka Honma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Survival Data ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Free Survival ◽  
The Impact ◽  
Line Chemotherapy

103 Background: The continuation of first-line chemotherapy or the maintenance chemotherapy has been selected for advanced gastric cancer patients who have not progressed after 4 to 6 cycles of first-line chemotherapy. However, survival data about those patients remains unclear. We retrospectively assessed the impact of response at 12 weeks on survival for advanced gastric cancer who received first-line chemotherapy. Methods: Eligible patients had unresectable advanced gastric adenocarcinoma and treated for the combination chemotherapy with fluoropyrimidine and platinum from January 2010 to December 2017 in our hospital. Patients with HER2 positive were excluded. Patients were divided into three groups (PR, SD, or PD group) according to response at 12 weeks of first-line chemotherapy, and their overall survival and progression-free survival were assessed. Results: The total number of the subject was 249 whose median overall survival (mOS) and progression-free survival (mPFS) were 13.8 and 5.4 months. Among 152 patients with measurable lesions, 58, 42, and 52 patients achieved PR, SD, and PD at 12 weeks. mOS was 16.7 months in the PR group, 9.8 months in the SD group, and 5.7 months in the PD group. mPFS was 7.1 months in the PR group, 4.5 months in the SD group, and 1.7 months in the PD group. Among 97 patients without measurable lesions, 90 patients achieved nonCR/nonPD at 12 weeks of first-line chemotherapy whose mOS and mPFS were 17.9 months and 9.2 months while those were 9.6 months and 1.9 months in the remaining 7 patients with PD at 12 weeks. Conclusions: There were clear differences in survival among PR, SD, and PD at 12 weeks in patients with measurable lesions while patients without measurable lesions obtaining nonCR/nonPD at 12 weeks showed similar OS and PFS to those with measurable lesion obtaining PR in first-line chemotherapy for advanced gastric cancer. [Table: see text]

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