Trastuzumab is recommended in conjunction with platinum and fluoropyrimidine-based chemotherapy for patients with HER2-positive advanced gastric cancer.

The Chinese population (28 vs 34) from the ToGA RCT was selected for subgroup analyses; resulting outcomes were more consistent with EVIDENCE for both OS (HR, 0.554; 95% CI, 0.261–1.174) and PFS (HR, 0.599; 95% CI, 0.324–1.107)....data from the ToGA and EVIDENCE studies showed the effectiveness of trastuzumab in Asian patients with HER2+ mGC in the RCT and real-world settings, respectively.

Herceptin in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of patients with HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction who have not received prior anticancer treatment for their metastatic disease.

...- HER2-positive AGC defined as either HER2 immunohistochemistry (IHC) 3+ or IHC 2+ and fluorescence in situ hybridization (FISH)+ with...

...- HER2 positive tumor (primary tumor or metastasis...

...- Locally advanced resectable HER2-positive gastric or esophagogastric junction adenocarcinoma (Sievert types I, II, III)...

...- HER2-positive primary or metastatic tumor as assessed by central laboratory...

...HER2 positive tumor (primary tumor or metastasis, HER2 positive as defined by IHC2+ and a confirmatory FISH+ result (HER2:CEP17 ratio ≥2), or by an IHC 3+ result) as assessed by the central laboratory....

...- Patients with histologically confirmed HER2 positive advanced gastric cancer through immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); -...

...Histologically confirmed diagnosis of HER2-positive breast or gastric cancer (defined as IHC 3+ or HER2 FISH amplification ratio >2.2) 3....

...HER2 positive tumour (primary tumour or metastasis) as assessed by the central laboratory....

...- Patients diagnosed with metastatic gastric or gastro-esophageal junction adenocarcinoma (HER2-positive), unresectable and histologically confirmed Measurable disease, following the new RECIST criteria,...

...- HER2-positive tumors...

...Patients with gastric cancer who met the diagnostic criteria and had positive HER-2 test and TNM stage IV; 2. ...

...HER2-positive: (IHC 3+ or IHC 2+ and FISH positive)....

...- Pathologically or cytologically confirmed metastatic or primary esophagogastric cancer HER2 positive status by FISH or IHC as currently being implemented for patients with esophagogastric cancer....

...HER2-positive tumor tissue (IHC 3 + or FISH positive) 3....

...HER2 positive: IHC 3+ or IHC 2+ plus FISH positive, HER2 negative: IHC 0/1+ or IHC 2+ plus FISH negative....

...The her-2 positive was detected by immunohistochemistry or Fluorescence in SituHybridization(FISH);...

...HER2 positive tumour (primary tumour or metastasis) defined as either IHC2+ and FISH+ or IHC3+ according to the gastric cancer scoring system for HER2 4....

...- HER2-positive tumor...

...HER2-positive tumor tissue (IHC 3 + or FISH positive)3. ...

...The her-2 positive was detected by immunohistochemistry or FISH; 3. ...

...Histologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic HER2+ GC or GEJ adenocarcinoma - Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS ≥ 1%), per central review. ...

As of data cutoff for the updated analysis (median follow-up 10·2 months [IQR 5·6-12·9]), a confirmed objective response was reported in 33 (42% [95% CI 30·8-53·4]) of 79 patients, including four (5%) complete responses and 29 (37%) partial responses, as assessed by independent central review...These clinically meaningful results support the use of trastuzumab deruxtecan as second-line therapy in patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer.

Meta-analysis results showed that trastuzumab in combination with chemotherapy achieved better outcomes on response rate (trastuzumab plus CFC vs CFC: odds ratio [OR] = 1.56, 95% confidence interval [CI] [1.17-2.09], I2 = 0%, P < .003; trastuzumab plus OT vs OT: OR = 2.97, 95% CI [1.74-5.09], I2 = 0%, P < .0001...The results of this study revealed that the efficacy of trastuzumab combined with chemotherapy was superior to that of chemotherapy alone for the treatment of HER2-PAGC.

We analysed the prevalence of Her2-positive metastatic gastric cancer, the overall survival (OS) and the progression-free survival (PFS) of these patients….In five of the patients the chemotherapy regimen used was the combination of 5-fluorouracil, cisplatin and trastuzumab...our median PFS (12 months) leads us to believe that much like the OS was better in the HER2-positive subgroup, so must the PFS improve in this subgroup.

...clinical characteristics and 1L tx were described by HER2 status for adult pts diagnosed with adv/met GC/GEJC/EAC from January 2011 to December 2020...a majority (65%) of HER2+ pts received trastuzumab…. Median OS for HER2+, HER2− and HER2un pts was 12.2, 9.8 and 7.6 months, respectively.

We evaluated the efficacy and safety of S-1 and oxaliplatin (100 mg/m2) (SOX100) combined with trastuzumab, a monoclonal antibody against HER2 for HER2-positive AGC....In the 25 patients evaluable for analysis, the 1-year survival rate was 70.8% [90% confidence interval (CI) = 55.5-86.1%], whereas the median OS, PFS, and ORR were 17.8 (95% CI 10.5-22.9) months, 7.6 (95% CI 5.0-10.9) months, and 75.0% (95% CI 53.3-90.2), respectively....SOX100 combined with trastuzumab was effective with a favorable safety profile in patients with HER2-positive AGC.

...138 patients who were given trastuzumab-based chemotherapy as first-line treatment and analyzed the relationship between clinical response rates and maintenance treatment status and survival outcomes...the median progression-free survival and overall survival were 10.2 and 16 months, respectively. Clinical response was obtained in 79% of patients. The median overall survival was 16.9 months in follow-up group and 19.0 months in the maintenance group in patients with clinical response.

A total of 138 patients with HER-2-positive advanced gastric cancer were divided into SOX group (SOX chemotherapy regimen combined with trastuzumab; n=69) and IP group (IP chemotherapy regimen combined with trastuzumab; n=69)….The disease control rate (DCR) was clearly better in SOX group than that in IP group... the follow-up results revealed that the PFS of patients was overtly longer in SOX group than that in IP group....Trastuzumab combined with SOX chemotherapy regimen has an obvious curative effect in the treatment of advanced gastric cancer, which prominently improves the quality of life of patients, lowers the serum tumor marker levels in patients, delays tumor progression, and results in tolerable adverse reactions.

EVIDENCE was a prospective, multicenter, non-interventional registry study evaluating the safety and effectiveness of trastuzumab in five cohorts of Chinese GC patients, stratified by HER2 status and trastuzumab treatment….Respective first-line progression-free survival (PFS1) was 8.2, 6.9, and 6.2 months; and respective first-line response rates (RR) were 51.7%, 18.4%, and 32.8%....Safety profiles were consistent with those known for trastuzumab and chemotherapy; trastuzumab treatment improved outcomes.

The patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection, were included. They received 3 cycles of oxaliplatin (100 mg/m2 intravenously day 1) plus capecitabine (850 mg/m2 orally days 1 to 14), trastuzumab (8 mg/kg intravenously day 1 in cycle 1, 6 mg/kg thereafter) every 21 days...After the 25 months follow-up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 58.0%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively.

This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution….With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%.

This Spanish, multicentre, open-label phase II trial evaluated the efficacy and toxicity of perioperative capecitabine, oxaliplatin and trastuzumab (XELOX-T) in patients with HER2-positive resectable GA or GEJA….Thirty-six patients were included....After a median follow-up of 24.1 months, 18-month DFS was 71% (95% confidence interval [CI], 53–83%); and an update after 102 months of follow-up showed a median OS of 79.9 months and a 60-month OS of 58% (95% CI, 40–73%).

Trastuzumab maintenance ± capecitabine after 6 cycles of trastuzumab plus combined chemotherapy treatment revealed efficacy and safety in non-progressive HER2-positive advanced gastric cancer.

Trastuzumab maintenance ± capecitabine after 6 cycles of trastuzumab plus combined chemotherapy treatment revealed efficacy and safety in non-progressive HER2-positive advanced gastric cancer.

We performed a retrospective cohort study to compare chemotherapies with or without trastuzumab among human epidermal growth factor receptor 2-positive (HER2 +) locally advanced GC patients in the AT and NAT settings, respectively....AT combined with trastuzumab showed a better overall survival (OS) over chemotherapy alone (p = 0.023). 

75 pts with a median follow up of 20.6 months, ORR was 70.7% (95% confidence interval (CI): 59.0–80.6) and the disease control rate was 93.3% (95% CI: 85.1–97.8)...OS and PFS (median) were 20.6 (95% CI: 15.9–29.2) and 8.8 (95% CI: 7.3–11.8) months...Tmab in combination with SOX exhibited promising therapeutic effects in pts with HER2-positive AGC.

We conducted an open-label, phase II trial in pts with chemo-naïve, HER2-positive AGC. Pts received S-1...oxaliplatin...trastuzumab...both OS and PFS were longer in pts with HER2 3+ (n=55) than in pts with 2+ (n=20) [OS, 25.9 vs.16.3 months; hazard ratio (HR), 0.59; 95% CI: 0.329–1.053; P=0.07; PFS, 9.8 vs. 7.0 months; HR, 0.72; 95% CI: 0.421–1.229; P=0.23].

OS of the standard and intensified group were 11.1 months (95% CI 8.3-13.9) and 15.2 months (95% CI 12.7-17.7), respectively (p = 0.03).

The objective response rate (ORR) of the 23 patients was 43.5% and the disease control rate (DCR) was 82.6%....The median overall survival (mOS) of ETS≥20% and ETS<20% were 26.8 months and 10.1 months, respectively, with statistical significance (P<0.001).

This phase II, multi-center, open-label, single arm study enrolled patients with HER2-positive AGC who had not received prior treatment for metastatic disease….The median PFS was 8.1 months (95% confidence interval [CI]: 5.6-12.8) and the median OS was 20.9 months (95% CI: 15.1-33.0). Response was evaluated in 59 patients. The ORR was 67.8%....We concluded that combination treatment with trastuzumab and DX was well-tolerated and highly effective...

PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months.

...to assess the efficacy and safety of T-mab + S-1 and oxaliplatin (T-SOX130) for HER2+ AGC or recurrent gastric cancer. T-SOX130 showed promising response and survival with a favorable safety profile and should be considered for patients with HER2+ AGC.

This is the multi-central, phase II study that is conducted in 10 Japanese institutions. Patients with HER2-positive AGC received S-1...oxaliplatin...trastuzumab...Median OS, PFS, were estimated as 20.6 (95% CI.14.8–30.6) and 9.4(95% CI.7.4-14.7) months, respectively....Trastuzumab in combination with SOX showed promising activity with well-tolerated toxicities in patients with HER2-positive AGC as well as other platinum and FUs.

Median PFS, TTF and OS was 7.0 (95%C.I.: 5.5–14.1), 5.7 (95%C.I.: 4.6–7.0) and 27.7 (95%C.I.: 15.6–) months, respectively....HER-SOX130 demonstrates promising response and survival with avourable safety profile. HER-SOX130 should be considered for the patients with HER2-positive AGC.

Combination of trastuzumab and docetaxel/capecitabine is a well-tolerated and highly effective regimen in patients with HER2-positive advanced gastric cancer

Combination of trastuzumab and docetaxel/capecitabine is a well-tolerated and highly effective regimen in patients with HER2-positive advanced gastric cancer

The median OS and PFS were significantly higher in those who demonstrated partial or complete response to trastuzumab combination treatment, and those who received more than 10 cycles of trastuzumab.

Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870-24,530) vs. 6.9 months (95% CI: 3.980-9.820), p = 0.016).

We conducted this phase II study to assess whether trastuzumab plus docetaxel was effective for patients with previously treated advanced HER2-positive gastric cancer….Partial response was seen in 3 patients among the 26 evaluated patients. The overall response rate was at 11.5% (90% confidence interval 1.2%-21.8%). The median progression-free survival was 3.2 months, the 6-month survival rate was 85%, and the median overall survival was 11.6 months.

The HER-2-positive patients were treated with trastuzumab combined with DOS regimen,while the HER-2-negative patients were treated with DOS regimen alone….In Trastuzumab + DOS group and DOS group, the objective response rate (ORR) was 66.0% and 52.8%, respectively, and the disease control rate (DCR) was 94.3% and 90.6%, respectively....the R0 resection rate in Trastuzumab + DOS group was significantly higher than that in DOS group. The pathological response rate (≥ grade 1b) was 80.0% and 60.4%, respectively, in the two groups, which was obviously higher in Trastuzumab + DOS group than that in DOS group.

We encountered a case of long-term survival after multidisciplinary treatments for HER2-positive advanced gastric cancer with multiple liver and lung metastases.

CONTRADICTING EVIDENCE: A 49-year-old female was diagnosed with stage IV GC with liver and lung metastasis in July 2017. She underwent gastrostomy, and the immunohistochemistry (IHC) result of postoperative tissue demonstrated HER2 (3+). She received first-line treatment of trastuzumab (440 mg), oxaliplatin (200 mg), and S-1 (40 mg)....After progression, she subsequently received trastuzumab (440 mg) plus oxaliplatin (200 mg) as second-line treatment. However, the patient developed resistance to trastuzumab after 12 months of treatment.

A 76-year-old male underwent distal gastrectomy for gastric cancer and pathological findings showed Stage IV (T4a, N3a, M1, H0, P0, CY1) with HER2 positivity….Fifth-line chemotherapy with trastuzumab was administered. After 4 courses, the lung metastases reduced and the left adrenal metastasis shrank from 46 mm to 33 mm. These results were consistent with a partial response on the Response Evaluation Criteria in Solid Tumors.

We retrospectively investigated the medical records of the patients with HER2 positive (immunohistochemistry (IHC) 3+ or IHC2+/fluorescence in-situ hybridization (FISH) positive) stage IV gastric cancer who were treated with trastuzumab-based chemotherapy...chemotherapy was given every 3 weeks. Capecitabine 1000 mg/m2 or S-1 80 mg/m2 was given orally twice a day for 14 days followed by a 1-week rest. On day 1, Cisplatin 80 mg/m2 was intravenously administered....Response rate was 63.6%, and the median OS, since the start of trastuzumab-based chemotherapy of those 11 patients was 31.5 months...

A man in his 60s who had epigastric pain was referred to our hospital and diagnosed with advanced type 3 gastric cancer with multiple liver metastases, cT4acN2cN1(H1), cStage Ⅳ(HER2 3+). He underwent chemotherapy using capecitabine, cisplatin(CDDP), and trastuzumab(T-mab)(XPT). The patient is alive without recurrence at 57 months after the initial treatment and 22 months after the last treatment.