An expert panel, consisting of the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology issued comprehensive, evidence-based guidelines for clinicians and pathologists regarding the testing of HER2 status for patients with gastroesophageal adenocarcinoma.
The FDA has lifted its clinical hold on trials exploring pacritinib, according to CTI BioPharma, the developer of the JAK2/FLT3 inhibitor.
Human epidermal growth factor receptor 2 (HER2)is currently the only biomarker available for selecting patients with advanced gastroesophageal adenocarcinoma (GEA) for targeted therapy. An expert panel, consisting of the College of American Pathologists (CAP), American Society for Clinical Pathology (ASCP), and the American Society of Clinical Oncology (ASCO), collectively recommended that all patients with GEA be tested for HER2 status prior to the initiation of HER2-directed therapies.
The panel issued comprehensive, evidence-based guidelines for clinicians and pathologists regarding the testing of HER2 status for patients with unresectable local-regional, recurrent, or metastatic GEA who are being considered for HER2-targeted therapy with trastuzumab (Herceptin).1
The guidelines contain 11 recommendations, divided by their targeted audience of practicing clinicians that treat patients with GEA and pathologists, as well as algorithms for tissue testing and decision making.
The authors noted that 7% to 38% of all GEAs demonstrate amplification and/or overexpression ofHER2,although more overexpression is noted for tumors in the gastroesophageal junction (GEJ) than for stomach cancer. HER2-directed therapy has shown increased survival over chemotherapy alone in patients withHER2-positive advanced GEA.
"As cancer care evolves to be increasingly personalized, this new guideline helps establish standards for when and how to accurately perform HER2 testing to guide treatment for gastroesophageal adenocarcinoma patients," Jaffer A. Ajani, MD, who represented ASCO on the panel, said in a statement.
The panel conducted a thorough literature review of 116 articles published between January 2008 and June 2015 and produced a draft set of guidelines in December 2015. The authors requested public feedback before the guidelines were finalized.
For clinicians, the guidelines recommend that all patients with advanced GEA who may be candidates for HER2-directed therapies first be tested for HER2 status using tumor tissue from a biopsy or resection specimen. As an alternative, FNA specimen testing was also deemed possible, though there is less evidence available to support this claim.
In the frontline, the guidelines recommend that patients be treated with a combination of HER2-targeted therapy, trastuzumab, and chemotherapy.
"We encourage clinical teams around the world to adopt these guidelines," Mary Kay Washington, MD, PhD, who represented the ASCP on the panel, said in a statement. "It will help improve patient care by ensuring that only patients likely to benefit from HER2‐directed therapy are treated with trastuzumab."
Currently, trastuzumab is the only FDA-approved HER2-targeted therapy for the treatment of previously untreated patients with metastatic gastric or GEJ adenocarcinoma with HER2 overexpression. The FDA approved the treatment in October 2010, when given in combination with cisplatin and a fluoropyrimidine, based on results of the ToGA trial.
In the open-label, randomized, controlled phase III trial, trastuzumab showed an overall survival benefit of 2.7 months when added to chemotherapy compared with chemotherapy alone. Trastuzumab was also found to be well tolerated in the trial.
For pathologists, the guidelines recommend testing for HER2 status using immunohistochemistry (IHC) first, which was backed by a high degree of evidence. If the IHC score (0-3+) is a 2+, the results were considered to be ambiguous and pathologists should try in situ hybridization (ISH) testing next, although the recommendation for further ISH testing was not as strong as for IHC testing.
The final recommendation statement mentioned that there was insufficient evidence at this time for or against genomic testing in advanced GEA patients. The authors found conflicting evidence for the prognostic nature ofHER2as an association betweenHER2amplification or overexpression and a poor prognosis in patients with GEA.
In the guidelines, the authors noted that the recommendations would be reviewed every 4 years and updated as needed.