Quick Take: Safety and Efficacy of the Addition of Lapatinib to Perioperative Chemotherapy for Resectable HER2-Positive Gastroesophageal Adenocarcinoma

Current international guidelines recommend a combination of perioperative chemotherapy and surgery in the treatment of operable gastroesophageal cancer. However, given high mortality rates in patients treated with contemporary perioperative chemotherapy, more clinically efficacious and less toxic regimens are needed. One potential strategy involves combining anti-HER2 agents, such as lapatinib, with neoadjuvant chemotherapy. In this randomized controlled open-label trial, 46 patients with HER2-positive operable gastroesophageal adenocarcinoma were assigned to receive either standard epirubicin, cisplatin, and capecitabine (sECX) or modified ECX plus lapatinib (mECX+L) to determine the safety of adding lapatinib to ECX chemotherapy and to establish a recommended treatment dose for a phase 3 trial. The primary outcome was the proportion of patients experiencing grade 3 or 4 diarrhea with mECX+L. Researchers found that the primary outcome occurred in more patients in the mECX+L group than in the sECX group (21% vs. 0%, respectively). In addition, more patients in the mECX+L arm stopped preoperative treatment early compared to patients in the sECX arm (15% vs. 4%, respectively). The most common preoperative toxic effect in both groups was neutropenia, and toxic effects more common in the mECX+L group included grade 1 or 2 stomatitis and vomiting. Postoperative complication rates were similar in each group, and the rate of toxic effects in the postoperative setting was similar to that in the preoperative setting. This study was limited by its small sample size. Importantly, the FLOT (fluorouracil, oxaliplatin, leucovorin, and docetaxel) regimen was adopted as the new perioperative standard of care in place of ECX after recruitment for this study had been completed, limiting the external validity of the study. Overall, this study suggests lapatinib in addition to ECX may be feasible for the treatment of HER2-positive gastroesophageal adenocarcinoma, although better regimens with less toxic effects, such as FLOT, are being investigated in combination with non-cardiotoxic agents in ongoing trials.

Click to read the study JAMA Oncology

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