Trastuzumab with chemotherapy

The double-blind, placebo-controlled, phase III, international KEYNOTE-811 trial (NCT03615326) studied dual pembrolizumab, trastuzumab, and chemotherapy (either 5-FU with cisplatin or CAPOX). A total of 434 patients with metastatic HER2-positive gastric adenocarcinoma were randomly assigned in a 1:1 ratio to receive either chemotherapy and trastuzumab (6 mg/kg every 3 weeks) with or without pembrolizumab (200 mg intravenously [IV] every 3 weeks).

The double-blind, placebo-controlled, phase III, international KEYNOTE-811 trial (NCT03615326) studied dual pembrolizumab, trastuzumab, and chemotherapy (either 5-FU with cisplatin or CAPOX). A total of 434 patients with metastatic HER2-positive gastric adenocarcinoma were randomly assigned in a 1:1 ratio to receive either chemotherapy and trastuzumab (6 mg/kg every 3 weeks) with or without pembrolizumab (200 mg intravenously [IV] every 3 weeks).

The objective response rate at the first interim analysis was 74.4% (95% CI, 66.2%–81.6%) for patients in the pembrolizumab arm and 51.9% (95% CI, 43.0%–60.7%) for patients in the placebo arm.[29][Level of evidence B3]

The double-blind, placebo-controlled, phase III, international KEYNOTE-811 trial (NCT03615326) studied dual pembrolizumab, trastuzumab, and chemotherapy (either 5-FU with cisplatin or CAPOX). A total of 434 patients with metastatic HER2-positive gastric adenocarcinoma were randomly assigned in a 1:1 ratio to receive either chemotherapy and trastuzumab (6 mg/kg every 3 weeks) with or without pembrolizumab (200 mg intravenously [IV] every 3 weeks).

Adverse events grade 3 or higher were observed in 57.1% of patients in the pembrolizumab arm (including 33.6% of patients with immune-related reactions) and 57.4% of patients in the placebo arm.

In the open-label, international, phase III Trastuzumab for Gastric Cancer trial (ToGA [NCT01041404]), patients with HER2-positive metastatic, inoperable locally advanced, or recurrent gastric or gastroesophageal junction cancer were randomly assigned to receive chemotherapy with or without the anti-HER2 monoclonal antibody trastuzumab.[30] HER2 positivity was defined as either 3+ by IHC or a HER2 to CEP17 ratio of 2 or more using FISH. Tumors from 3,665 patients were tested for HER2; of the patients, 810 were positive (22%) and 594 met eligibility criteria for randomization. Chemotherapy consisted of cisplatin plus 5-FU or capecitabine chosen at the investigator’s discretion. The study treatment was administered every 3 weeks for six cycles, and trastuzumab was continued every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Crossover to trastuzumab at disease progression was not permitted.

In the open-label, international, phase III Trastuzumab for Gastric Cancer trial (ToGA [NCT01041404]), patients with HER2-positive metastatic, inoperable locally advanced, or recurrent gastric or gastroesophageal junction cancer were randomly assigned to receive chemotherapy with or without the anti-HER2 monoclonal antibody trastuzumab.[30] HER2 positivity was defined as either 3+ by IHC or a HER2 to CEP17 ratio of 2 or more using FISH. Tumors from 3,665 patients were tested for HER2; of the patients, 810 were positive (22%) and 594 met eligibility criteria for randomization. Chemotherapy consisted of cisplatin plus 5-FU or capecitabine chosen at the investigator’s discretion. The study treatment was administered every 3 weeks for six cycles, and trastuzumab was continued every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Crossover to trastuzumab at disease progression was not permitted.

The median OS was 13.8 months (95% CI, 12–16) in patients assigned to trastuzumab and 11.1 months (95% CI, 10–13) in patients assigned to chemotherapy alone (HR, 0.74; 95% CI, 0.60–0.91; P = .0046).[30][Level of evidence A1]

In the open-label, international, phase III Trastuzumab for Gastric Cancer trial (ToGA [NCT01041404]), patients with HER2-positive metastatic, inoperable locally advanced, or recurrent gastric or gastroesophageal junction cancer were randomly assigned to receive chemotherapy with or without the anti-HER2 monoclonal antibody trastuzumab.[30] HER2 positivity was defined as either 3+ by IHC or a HER2 to CEP17 ratio of 2 or more using FISH. Tumors from 3,665 patients were tested for HER2; of the patients, 810 were positive (22%) and 594 met eligibility criteria for randomization. Chemotherapy consisted of cisplatin plus 5-FU or capecitabine chosen at the investigator’s discretion. The study treatment was administered every 3 weeks for six cycles, and trastuzumab was continued every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Crossover to trastuzumab at disease progression was not permitted.

There was no significant difference in rates of any adverse event, and cardiotoxic effects were equally rare in both arms.