Dataset Information

Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer.

ABSTRACT: There is currently no clinical data regarding the efficacy of trastuzumab treatment for the progression of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) occurring during trastuzumab-based chemotherapy. The aim of this study was to retrospectively examine the clinical benefits of trastuzumab for HER2-positive AGC patients who progressed during first-line trastuzumab-based chemotherapy. Among the 108 patients treated with trastuzumab combined with fluoropyrimidine and cisplatin as first-line therapy, 46 HER2-positive AGC patients who received cytotoxic agents with or without trastuzumab subsequent to disease progression were included. Of these, the efficacy and safety outcomes of 26 patients who continued trastuzumab were compared with those of the 20 patients who discontinued trastuzumab. No difference in response rate (18.2 vs. 15.8%, P=1.00) was observed between the two groups. Progression-free survival (PFS) time was numerically longer in the chemotherapy combination with trastuzumab group than in the chemotherapy combination without trastuzumab group (median, 4.0 vs. 2.3 months), with no significance [hazard ratio (HR), 0.63; P=0.14]. In the subset analysis, continuation of trastuzumab significantly improved PFS time in selected subgroups of patients with tumors exhibiting HER2 expression scores of 3+ (HR, 0.41; P=0.04), intestinal-type histology (HR, 0.32; P<0.01), and a first PFS time of >6 months (HR, 0.44; P=0.04). The survival times for the trastuzumab beyond progression (TBP) and non-TBP groups were similar (HR, 1.06; P=0.88), with equivalent overall survival times in the subgroups with immunohistochemistry scores of 3+ (HR, 0.97; P=0.94), intestinal-type histology (HR, 0.53; P=0.19), and a first PFS time of >6 months (HR, 0.62; P=0.31). There were no differences in the incidence rates of toxicity, including cardiac dysfunction, between the two groups. The study results suggest that selected HER2-positive AGC patients may benefit from trastuzumab continuation during first progression, and further prospective studies are warranted.

SUBMITTER: Narita Y

PROVIDER: S-EPMC5530221 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundDespite the wide spread use of trastuzumab in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic gastric cancer patients, its optimal duration of administration beyond first-line disease progression is unknown. In HER2 overexpressing metastatic breast cancer, trastuzumab continuation beyond first-line disease progression has shown improvement in time to progression (TTP) without an increased risk of treatment related toxicity.MethodsHER2-overexpressing metastatic gastric cancer patients were identified from our database between January 2010 and December 2014. We retrospectively reviewed the medical records of 43 patients who received trastuzumab in combination with chemotherapy as first-line and continued trastuzumab beyond disease progression.ResultsForty-three cases were identified, 27 males (62.8%), median age of the patients was 58 years. Thirty-five (81.4%) presented with stage 4 as their initial presentation. Eighty one percent had 3+ HER2 overexpression by immunohistochemistry (IHC) and 18% had 2+ HER2 overexpression confirmed by fluorescence in situ hybridization (FISH). Thirteen (52%) were moderately differentiated, 16 (37.1%) were poorly differentiated. The most common sites of metastasis were liver 35 (81.4%) and lung 14 (32.5%). The most commonly used first-line regimen was oxaliplatin, 5-fluorouracil (5-FU), and trastuzumab in 22 (51.1%) patients. Twenty-five (58.1%) patients received irinotecan, 5-FU and trastuzumab in the second-line. Progression-free survival (PFS) was 5 months (95% CI: 4.01-5.99 months). Five patients are still alive and excluded from calculating the median overall survival (OS) which was 11 months (range, 5-53 months) for the remaining 20 subjects of this second-line group. Trastuzumab was not discontinued due to side effects in any of the study population.ConclusionsIn conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in patients with HER2-overexpressing metastatic gastric cancer is feasible and safe. Randomized studies are warranted.

Project description:UnlabelledWomen with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are candidates for treatment with the anti-HER2 antibody trastuzumab. Assessment of HER2 status in recurrent disease is usually made by core needle biopsy of a single lesion, which may not represent the larger tumor mass or other sites of disease. Our long-range goal is to develop PET of radiolabeled trastuzumab for systemically assessing tumor HER2 expression and identifying appropriate use of anti-HER2 therapies. The purpose of this study was to evaluate PET/CT of (64)Cu-DOTA-trastuzumab for detecting and measuring tumor uptake of trastuzumab in patients with HER2-positive metastatic breast cancer.MethodsEight women with biopsy-confirmed HER2-positive metastatic breast cancer and no anti-HER2 therapy for 4 mo or longer underwent complete staging, including (18)F-FDG PET/CT. For 6 of the 8 patients, (64)Cu-DOTA-trastuzumab injection (364-512 MBq, 5 mg of trastuzumab) was preceded by trastuzumab infusion (45 mg). PET/CT (PET scan duration 1 h) was performed 21-25 (day 1) and 47-49 (day 2) h after (64)Cu-DOTA-trastuzumab injection. Scan fields of view were chosen on the basis of (18)F-FDG PET/CT. Tumor detection sensitivity and uptake analyses were limited to lesions identifiable on CT; lesions visualized relative to adjacent tissue on PET were considered PET-positive. Radiolabel uptake in prominent lesions was measured as maximum single-voxel standardized uptake value (SUVmax).ResultsLiver uptake of (64)Cu was reduced approximately 75% with the 45-mg trastuzumab predose, without significant effect on tumor uptake. The study included 89 CT-positive lesions. Detection sensitivity was 77%, 89%, and 93% for day 1, day 2, and (18)F-FDG, respectively. On average, tumor uptake was similar for (64)Cu-DOTA-trastuzumab and (18)F-FDG (SUVmax and range, 8.1 and 3.0-22.5 for day 1 [n = 48]; 8.9 and 0.9-28.9 for day 2 [n = 38]; 9.7 and 3.3-25.4 for (18)F-FDG [n = 56]), but same-lesion SUVmax was not correlated between the 2 radiotracers. No toxicities were observed, and estimated radiation dose from (64)Cu-DOTA-trastuzumab was similar to (18)F-FDG.Conclusion(64)Cu-DOTA-trastuzumab visualizes HER2-positive metastatic breast cancer with high sensitivity and is effective in surveying disseminated disease. A 45-mg trastuzumab predose provides a (64)Cu-DOTA-trastuzumab biodistribution favorable for tumor imaging. (64)Cu-DOTA-trastuzumab PET/CT warrants further evaluation for assessing tumor HER2 expression and individualizing treatments that include trastuzumab.

Dataset Information

Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets