Trial Outcomes & Findings for Human Epidermal Growth Factor Receptor 2 (HER-2) Status in Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma (NCT NCT02731313)

Last Updated: 2016-10-28

Results Overview

Positive HER-2 status was defined as either immunohistochemistry (IHC) score of 3+ or IHC score 2+/in situ hybridization (ISH) score +, as per the trastuzumab Summary of Product Characteristics (SPC). The HER-2 status in tumor specimens was determined using the pathologist's choice of IHC and ISH techniques in local laboratories, and using IHC 4B5 and silver ISH (SISH) in centralized laboratories. The kappa coefficient was used to evaluate the true concordance between the HER-2 status determined by local and centralized laboratories. The kappa coefficient value was interpreted according to the Landis and Koch classification as follows: a) less than (\<) 0: less than chance agreement, b) 0.01-0.20: slight agreement, c) 0.21-0.40: fair agreement, d) 0.41-0.60: moderate agreement, e) 0.61-0.80: substantial agreement, and f) 0.81-0.99: almost perfect agreement.

Recruitment status

COMPLETED

Target enrollment

420 participants

Primary outcome timeframe

At enrollment

Results posted on

2016-10-28

Participant Flow

A total of 448 tumor specimens originating from 420 participants were assessed for inclusion in the study. Of these 448 specimens, 54 were excluded from analysis. 394 tumor specimen were included in the study which were derived from a population of 367 participants. This population (n=367) is reported in this study.

Participant milestones

Participant milestones
Measure	Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma Tumor samples with histologically confirmed gastric or GEJ adenocarcinoma, any stage, were collected and analyzed. No study visits or interventions were planned
Overall Study STARTED	367
Overall Study COMPLETED	367
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Human Epidermal Growth Factor Receptor 2 (HER-2) Status in Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma Samples n=367 Participants Tumor samples with histologically confirmed gastric or GEJ adenocarcinoma, any stage, were collected and analyzed. No study visits or interventions were planned Trastuzumab: Trastuzumab was not administered in this study. This study informs future trastuzumab treatment decisions.
Age, Continuous	66.4 years STANDARD_DEVIATION 13.2 • n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants
Sex: Female, Male Male	254 Participants n=5 Participants

PRIMARY outcome

Timeframe: At enrollment

Population: The specimens' population is defined as all specimens for which at least one IHC and/or ISH test was done in the centralized laboratory, without any reasons for exclusion.

Outcome measures

Outcome measures
Measure	Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma n=394 Tumor specimens Tumor samples with histologically confirmed gastric or GEJ adenocarcinoma, any stage, were collected and analyzed. No study visits or interventions were planned
Simple Kappa Coefficient of Human Epidermal Growth Factor Receptor 2 (HER-2) Status Between Local and Centralized Laboratory Assessments	0.69 kappa coefficient Interval 0.6 to 0.78

SECONDARY outcome

Timeframe: At enrollment

Population: The participants' sub-population being all participants from the specimen population, which is defined as all specimens for which at least one IHC and/or ISH test was done in the centralized laboratory, without any reasons for exclusion. Here, 'n' is number of participants with available data for this outcome measure.

Outcome measures

Outcome measures
Measure	Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma n=366 Participants Tumor samples with histologically confirmed gastric or GEJ adenocarcinoma, any stage, were collected and analyzed. No study visits or interventions were planned
Cancer Characteristics: Percentage of Participants With Initial Location of Adenocarcinoma in Stomach Versus Esogastric Location Stomach	59.6 percentage of participants
Cancer Characteristics: Percentage of Participants With Initial Location of Adenocarcinoma in Stomach Versus Esogastric Location Esogastric junction	40.4 percentage of participants

SECONDARY outcome

Timeframe: At enrollment

The Lauren classification is based on examination of histologic specimens under the microscope and divides adenocarcinoma of the stomach into 3 types: 1) Diffuse type: tumor cells are poorly differentiated, behave aggressively and tend to scatter throughout the stomach (rather than form glands). This type metastasizes to other parts of the body much quicker than intestinal type tumors, 2) Intestinal type: tumor cells are well differentiated, grow slowly and tend to form glands, 3) Mixed type: this type is made up of both intestinal and diffuse types.

Outcome measures

Outcome measures
Measure	Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma n=365 Participants Tumor samples with histologically confirmed gastric or GEJ adenocarcinoma, any stage, were collected and analyzed. No study visits or interventions were planned
Cancer Characteristics: Percentage of Participants With Samples in Each of the Histologic Type Lauren's Classifications, Including Diffuse Type, Intestinal and Mixed Diffuse type	29.6 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Histologic Type Lauren's Classifications, Including Diffuse Type, Intestinal and Mixed Intestinal type	54.8 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Histologic Type Lauren's Classifications, Including Diffuse Type, Intestinal and Mixed Mixed type	9.6 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Histologic Type Lauren's Classifications, Including Diffuse Type, Intestinal and Mixed Non-evaluable	0.3 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Histologic Type Lauren's Classifications, Including Diffuse Type, Intestinal and Mixed Other types	5.8 percentage of participants

SECONDARY outcome

Timeframe: At enrollment

The TNM stage system includes information about the size of the primary tumor (T), whether the cancer has spread to nearby lymph nodes (N) and whether the cancer has metastasized to other parts of the body (M). In the T classification TX indicates that the main tumor cannot be measured, T1, T2, T3 and T4 refer to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. In the N classification NX indicates that the cancer in nearby lymph nodes cannot be measured, N0 indicates that there is no cancer in nearby lymph nodes, N1, N2 and N3 refer to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer. In the M classification MX indicates that the metastasis cannot be measured, M0 indicates that the cancer has not spread to other parts of the body and M1 indicates that the cancer has spread to other parts of the body.

Outcome measures

Outcome measures
Measure	Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma n=366 Participants Tumor samples with histologically confirmed gastric or GEJ adenocarcinoma, any stage, were collected and analyzed. No study visits or interventions were planned
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages T1	9.8 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages T2	8.2 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages T4	12.6 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages Tx	43.4 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages N0	23.0 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages N1	10.7 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages N2	12.0 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages N3	9.0 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages Nx	45.4 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages M0	18.6 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages M1	5.5 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages Mx	76.0 percentage of participants
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages T3	26.0 percentage of participants

SECONDARY outcome

Timeframe: At enrollment

Population: The specimens' population is defined as all specimens for which at least one IHC and/or ISH test was done in the centralized laboratory, without any reasons for exclusion. Here, 'n' is number of specimens with available data for this outcome measure.

Positive HER-2 status was defined as either immunohistochemistry (IHC) score of 3+ or IHC score 2+/in situ hybridization (ISH) score +, as per the trastuzumab Summary of Product Characteristics (SPC). The HER-2 status in tumor specimens was determined using IHC 4B5 and silver ISH (SISH) in centralized laboratories. The weighted kappa coefficient was used to evaluate the true concordance between the HER-2 status determined by IHC 4B5 and SISH. The weighted kappa coefficient value was interpreted according to the Landis and Koch classification as follows: a) less than (\<) 0: less than chance agreement, b) 0.01-0.20: slight agreement, c) 0.21-0.40: fair agreement, d) 0.41-0.60: moderate agreement, e) 0.61-0.80: substantial agreement, and f) 0.81-0.99: almost perfect agreement.

Outcome measures

Outcome measures
Measure	Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma n=393 Specimens Tumor samples with histologically confirmed gastric or GEJ adenocarcinoma, any stage, were collected and analyzed. No study visits or interventions were planned
Weighted Kappa Coefficient Between Immunohistochemistry (IHC) 4B5 and Silver in Situ Hybridization (SISH) Techniques for HER-2 Testing in Centralized Laboratories	0.64 weighted kappa coefficient Interval 0.56 to 0.72

Adverse Events

Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER