Trastuzumab deruxtecan or ramucirumab plus paclitaxel in gastric cancer

Data from the phase 3 DESTINY-Gastric04 trial, recently published on The New England Journal of Medicine, showed an overall survival significantly longer with a second line therapy with trastuzumab deruxtecan than with ramucirumab plus paclitaxel.

Authors enrolled 494 patients with locally or centrally confirmed HER2-positive unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma on a tumor biopsy conducted after progression during trastuzumab-based therapy, to exclude patients who had loss of HER2 after trastuzumab-based therapy. The trial compared second-line trastuzumab deruxtecan (6.4 mg kg) with ramucirumab plus paclitaxel. The median overall survival was 14.7 months with trastuzumab deruxtecan versus 11.4 months with ramucirumab plus paclitaxel; a confirmed objective response was seen in 44.3% of the patients in the trastuzumab deruxtecan group versus 29.1% of those in the ramucirumab–paclitaxel group. The incidence of drug-related adverse events of grade 3 or higher was 50% and 54.1%, respectively. «The phase 3 DESTINY-Gastric04 trial showed significantly prolonged overall survival with a HER2-directed therapy as second-line therapy in patients with HER2-positive unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma», authors say. «The improved efficacy of trastuzumab deruxtecan over ramucirumab plus paclitaxel was further supported by significant improvements in secondary endpoints, including progression-free survival and objective response. This trial showed that trastuzumab deruxtecan had superior efficacy as second-line therapy over ramucirumab plus paclitaxel in patients with HER2-positive unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. These results warrant further evaluation of trastuzumab deruxtecan in the context of first-line therapy», authors conclude.