Adding dual HER2-targeted therapy to neoadjuvant chemoradiotherapy is a well tolerated and efficacious treatment strategy in patients with resectable esophageal adenocarcinoma positive for this receptor, a multicenter phase 2 TRAP trial suggests.
Survival of esophageal cancer with neoadjuvant chemoradiotherapy alone remains poor, note senior investigator Hanneke W. M. van Laarhoven, MD, PhD, Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, and coinvestigators. But 15%-43% of tumors are positive for HER2, raising the possibility that targeted therapy could improve outcomes for some.
The investigators enrolled in the TRAP trial 40 patients with resectable HER2-positive adenocarcinoma of the esophagus or gastroesophageal junction. Among the patients, 78% were men, and the median age was 63 years. Planned treatment for all patients consisted of neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in weeks 1 through 5, plus both trastuzumab (Herceptin) and pertuzumab (Perjeta) in weeks 2 through 13, then surgery in week 14.
Trial results reported in the Journal of Clinical Oncology showed that 83% of the patients completed treatment with trastuzumab and pertuzumab, meeting the predefined 80% threshold for feasibility of this treatment.
There were no unexpected safety events. Some 48% of patients had grade 3 or worse adverse events (mainly diarrhea and dysphagia), and 28% had serious adverse events (mainly vomiting, nausea, and gastrointestinal hemorrhage).
Of the 38 patients who underwent surgery, all achieved a complete (R0) resection and 34% achieved a pathologic complete response.
With a median follow-up of 32.1 months, the 3-year rates of progression-free survival and overall survival were 72% and 71%, respectively.
Compared with a cohort of similar patients from the Netherlands Cancer Registry who received conventional neoadjuvant chemoradiotherapy and were matched on propensity score (but not HER2 status), the trial patients had a significantly lower risk of death (hazard ratio, 0.58; 95% confidence interval, 0.34-0.97).