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ASCO 2016 – June 3-7, Chicago, Illinois, USA
Congress Highlights by Dr Elizabeth Smyth
Two important studies were presented at ASCO for gastric cancer, one in the peri-operative setting, and another for patients with advanced disease.
The CRITICS study was presented by Dr Marcel Verheij. This was a multicentre, randomised phase III study for patients with Ib-Iva gastric resectable gastric cancer. All patients were initially treated with pre-operative chemotherapy containing epirubicin, cisplatin or oxaliplatin and capecitabine. Patients were randomly assigned following their surgery to the same chemotherapy regimen or chemoradiotherapy (45Gy in 25 fractions with concurrent low dose cisplatin and capecitabine). The primary endpoint of the study, 5 year overall survival, was similar for patients in both arms (40.8% for chemotherapy and 40.9% for chemoradiotherapy). Median overall survival was 3.5 years vs 3.3 years respectively. Surgical quality was good in the study; at least 87% of patients had a D1+ dissection and the median number of lymph nodes removed was twenty. However, it was notable that many patients did not complete postoperative treatment (47% vs 52%) for chemotherapy and chemoradiotherapy arms respectively.
These data suggest that further intensification of postoperative adjuvant treatment with gastric cancer does not improve overall survival. While it is possible that there may be subsets of high risk patients (node positive for example) who may benefit from additional treatment, this is difficult to deliver in patients who have undergone gastrectomy, and therefore increasing the intensity of treatment at that time may be not be practical. The addition of targeted therapies and immunotherapy to peri-operative treatment may be more fruitful in future, due to non-overlapping toxicities with chemotherapy and/or radiotherapy.
Dr Salah Al-Batran presented the results of the FAST trial which demonstrated encouraging results for patients with Claudin 18.2 positive advanced gastric and gastroesophageal cancer treated with IMAB362 in a phase II study. IMAB362 is a monoclonal antibody against claudin 18.2 which is a tight junction protein expressed by several GI tumours including gastroesophageal, pancreatic and biliary cancers. Patients were eligible if they had at least 40% Claudin 18.2 expression on their tumours at an immunohistochemical level of 2 or greater. One hundred and sixty-one patients were treated in the primary comparison, 77 in an IMAB362 plus EOX arm and 84 with EOX alone. Patients treated with IMAB362 had superior progression free survival compared to patients treated with EOX alone (7.9m vs 4.8m) (p=0.002), meeting the primary endpoint for the study. Overall survival was also improved for the experimental arm (13.2m IMAB362 plus EOX vs 8.4months EOX alone, HR 0.51, 95% CI (0.36 – 0.73), p=0.0001). Overall survival was particularly improved for patients with the highest levels of Claudin 18.2 expression (16.7m vs 9.0m, HR.045, p <0.0005). The most frequently reported toxicity was nausea and vomiting, with also an increase in neutropenia demonstrated.
The results of the FAST study are very encouraging for advanced gastroesophageal cancer patients who express claudin 18.2. However, this is a phase II trial, and further exploration in a phase III trial is warranted as encouraging phase II results are not always replicated in the phase III setting. The failure of rilotumumab is the most recent example of this for patients with gastric cancer. Nonetheless, with limited additive toxicity and results for high expressers of claudin 18.2 comparable to HER2 high expressors treated with chemotherapy plus trastuzumab, this is definitely an exciting development.