TRAstuzumab and Pertuzumab for HER2+ Resectable Oesophageal Cancer

Inclusion Criteria: * Histologically proven adenocarcinoma of the esophagus or gastroesophageal junction, T1N+M0; or T2-T4a N0 or N+ M0). * HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter in combination with ISH+, as assessed by the local laboratory on a primary tumor biopsy. HER2 status needs to be confirmed by the central laboratory, but does not affect start of treatment. * Surgical resectability, as determined during multidisciplinary meeting. Tumors that cannot be passed with an endoscope for endoscopic ultrasound are eligible if all other criteria are fulfilled. * If the tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. * Age ≥ 18. * ECOG performance status 0 or 1 (cf. Appendix A). * Adequate hematological, renal and hepatic functions defined as: * Neutrophils ≥ 1.5 x 109/L * Platelets ≥ 100 x 109/L * Hemoglobin ≥ 5.6 mmol * Total bilirubin ≤ 1.5 x upper normal limit * Creatinine clearance (Cockroft) \> 60 ml/min * Adequate left ventricular ejection fraction defined as an LVEF of ≥55% determined by transthoracic echocardiography or MUGA. * Written, voluntary informed consent * Patients must be accessible to follow up and management in the treatment center Exclusion Criteria: * T1N0 tumors or in situ carcinoma. * Past (within 5 years) or current history of malignancy other than entry diagnosis which has a worse expected prognosis than the current esophageal cancer. * Previous chemotherapy, radiotherapy, treatment with an anti-HER2 antibody or with small molecule HER2 inhibitors for esophageal cancer or for any other cancer within 6 months of diagnosis of esophageal cancer. * Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor. * Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. * Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. * Not willing to use highly effective methods of contraception (per institutional standard) during treatment (male or female) and for 6 months after the end of treatment. * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery. * Pulmonary fibrosis and/or severely impaired lung function (FEV1 \< 1,5L) precluding major surgery. * Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine. * Dementia or altered mental status that would prohibit the understanding and giving of informed consent * Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding. * Evidence of interstitial lung disease or active, non-infectious pneumonitis. * Active infection requiring systemic therapy which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment. * Evidence of acute or chronic infection with hepatitis B, C or HIV. * History of prior allogeneic stem cell or solid organ transplantation. * Pre-existing motor or sensory neurotoxicity greater than or equal to CTC AE grade 2.