Increased assessment of HER2 in metastatic gastroesophageal cancer patients: a nationwide population-based cohort study.

BACKGROUND: Addition of trastuzumab to first-line palliative chemotherapy in gastroesophageal cancer patients with HER2 overexpression has shown to improve survival. Real-world data on HER2 assessment and administration of trastuzumab are lacking. The aim of this study was to assess HER2 testing, trastuzumab administration, and overall survival (OS) in a nationwide cohort of metastatic gastroesophageal cancer patients. METHODS: Data of patients with synchronous metastatic gastroesophageal adenocarcinoma diagnosed in 2010-2016 that received palliative systemic treatment (n = 2846) were collected from the Netherlands Cancer Registry and Dutch Pathology Registry. The ToGA trial criteria were used to determine HER2 overexpression. Proportions of HER2 tested patients were analyzed between hospital volume categories using Chi-square tests, and over time using trend analysis. OS was tested using the Kaplan Meier method with log rank test. RESULTS: HER2 assessment increased annually, from 18% in 2010 to 88% in 2016 (P < 0.01). Median OS increased from 6.9 (2010-2013) to 7.9 months (2014-2016; P < 0.05). Between the hospitals, the proportion of tested patients varied between 29-100%, and was higher in high-volume hospitals (P < 0.01). Overall, 77% of the HER2 positive patients received trastuzumab. Median OS was higher in patients with positive (8.8 months) and negative (7.4 months) HER2 status, compared to non-tested patients (5.6 months; P < 0.05). CONCLUSION: Increased determination of HER2 and administration of trastuzumab have changed daily practice management of metastatic gastroesophageal cancer patients receiving palliative systemic therapy, and possibly contributed to their improved survival. Further increase in awareness of HER2 testing and trastuzumab administration may improve quality of care and patient outcomes.

Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial.

BACKGROUND: Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4-6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. METHODS: This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. DISCUSSION: The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. TRIAL REGISTRATION: ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016-001783-12, April 202,016).

Immuno-Histochemical Assessment of HER2NEU Expression in Gastric Adenocarcinoma in North Karnataka, India

Background and Objectives: Gastric cancer is the fourth most common cancer worldwide and ranks fifth in India. Surgical resection is curative in early stage gastric cancers. Most of the gastric cancers are diagnosed at an advanced stage necessitating multimodality treatment strategies. Based on the ToGA trial, the international regulatory agencies have recently approved trastuzumab in locally advanced and metastatic gastric and gastroesophageal adenocarcinomas expressing HER2. Since there are limited studies from India and no published data available from this part of North Karnataka, we undertook this study to evaluate the frequency of expression of HER2 in gastric and gastroesophageal adenocarcinomas and to correlate it with various clinicopathological variables. Methodology: The study was conducted in the Department of Pathology, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka from May 2012 to January 2016. The samples included both endoscopic biopsies and gastrectomies. Histopathological slides from 70 cases were reviewed. Immunohistochemical staining for HER2 was performed in all the cases and Hoffman's gastric cancer scoring system was employed. The results of HER2 expression was correlated with various clinicopathological parameters. Results: HER2 positivity was seen in 16/70 cases (23%). 6 cases (8.5%) were equivocal and 48/70 cases (68.5%) were HER2 negative. HER2 positivity was more common in GEJ cancers and intestinal type of adenocarcinoma. However, it did not correlate with age, gender, grade and stage. Conclusion: HER2 positivity was noted in 23% of the cases. 23.4% of intestinal type and 21.7% of diffuse type were HER2 positive. HER2 positivity did not significantly depend on age, gender, tumour type, grade and stage. Hence, HER2 remains as an independent biomarker and should be tested in all patients of gastric cancer regardless of the clinicopathological findings for offering a personalized treatment.

Assessment of EGFR and ERBB2 (HER2) in Gastric and Gastroesophageal Carcinomas: EGFR Amplification is Associated With a Worse Prognosis in Early Stage and Well to Moderately Differentiated Carcinoma.

Epidermal growth factor receptor 1 (EGFR) and erb-b2 receptor tyrosine kinase 2 (ERBB2/HER2) are frequently dysregulated in human cancers. We analyzed EGFR and ERBB2 status in 105 gastric and gastroesophageal junction carcinoma and their clinicopathologic features. For EGFR, 92 (88%) tumors were scored as 0, 2 (2%) as 1+, 7 (7%) as 2+, and 4 (3%) as 3+ by immunohistochemistry (IHC) and 4 (4%) tumors showed EGFR amplification by fluorescence in situ hybridization (FISH). For ERBB2, 90 (86%) tumors were scored as 0, 4 (4%) as 1+, 6 (6%) as 2+, and 5 (5%) as 3+ by IHC and 12 (12%) showed ERBB2 amplification by FISH. The concordance rate between IHC and FISH of EGFR was 98.1% (P<0.001) and of ERBB2 was 93.3% (P<0.001). Most tumors with ERBB2 amplification were tubular adenocarcinoma (N=11, P=0.02) and Lauren intestinal type (N=12, P=0.016). There was no statistically significant difference between EGFR amplification and tumor classification. EGFR amplification had significant impact on overall survival in certain subgroups: early stages (stages I and II) (P<0.001), well to moderately differentiated tumors (P=0.001), and fewer regional lymph node metastasis (pN1) (P=0.001). ERBB2 status had little predictive value on overall survival. In conclusion, this study showed ERBB2 amplification was significantly observed in tubular adenocarcinoma and Lauren intestinal-type carcinoma. The IHC scoring criteria for ERBB2 can be applied to EGFR. EGFR amplification had associated with poor prognosis in early, well to moderately differentiated carcinoma.

Critical Assessment of Endoscopic Techniques for Gastroesophageal Reflux Disease.

Over the past 2 decades, a number of new endoscopic techniques have been developed for management of gastroesophageal (GE) reflux disease symptoms as alternatives to medical management and surgical fundoplication. These devices include application of radiofrequency treatment (Stretta), endoscopic plication (EndoCinch, Plicator, Esophyx, MUSE), and injection of bulking agents (Enteryx, Gatekeeper, Plexiglas, Duragel). Their goal was symptom relief through reduction of tissue compliance and enhancement of anatomic resistance at the GE junction. In this review, we critically assess the research behind the efficacy, safety, and durability of these treatments to better understand their roles in contemporary GE reflux disease management.