Immunotherapy for patients who relapse after one prior line of standard therapy

The open-label phase II KEYNOTE-181 study (NCT02564263) included 628 patients with advanced or metastatic squamous cell carcinoma (n = 401) or adenocarcinoma (n = 227) of the esophagus that progressed after one prior therapy. Patients were randomly assigned (1:1) to receive either pembrolizumab (200 mg every 3 weeks for up to 2 years) or chemotherapy (investigator’s choice of paclitaxel, docetaxel, or irinotecan). Primary end points were OS in patients with a PD-L1 CPS of 10 or more, OS in patients with squamous cell carcinoma, and OS in all patients (one-sided alpha, 0.9%, 0.8%, and 0.8%, respectively).[51]

The open-label phase II KEYNOTE-181 study (NCT02564263) included 628 patients with advanced or metastatic squamous cell carcinoma (n = 401) or adenocarcinoma (n = 227) of the esophagus that progressed after one prior therapy. Patients were randomly assigned (1:1) to receive either pembrolizumab (200 mg every 3 weeks for up to 2 years) or chemotherapy (investigator’s choice of paclitaxel, docetaxel, or irinotecan). Primary end points were OS in patients with a PD-L1 CPS of 10 or more, OS in patients with squamous cell carcinoma, and OS in all patients (one-sided alpha, 0.9%, 0.8%, and 0.8%, respectively).[51]

At final analysis, conducted 16 months after the last patient was randomly assigned, OS was prolonged in patients with a CPS of 10 or more who received pembrolizumab versus chemotherapy (median OS, 9.3 vs. 6.7 months; HR, 0.69; 95% CI, 0.52–0.93; P = .0074).[51][Level of evidence A1]

The open-label phase II KEYNOTE-181 study (NCT02564263) included 628 patients with advanced or metastatic squamous cell carcinoma (n = 401) or adenocarcinoma (n = 227) of the esophagus that progressed after one prior therapy. Patients were randomly assigned (1:1) to receive either pembrolizumab (200 mg every 3 weeks for up to 2 years) or chemotherapy (investigator’s choice of paclitaxel, docetaxel, or irinotecan). Primary end points were OS in patients with a PD-L1 CPS of 10 or more, OS in patients with squamous cell carcinoma, and OS in all patients (one-sided alpha, 0.9%, 0.8%, and 0.8%, respectively).[51]

Among patients with squamous cell carcinoma, the median OS was 8.2 months for patients who received pembrolizumab and 7.1 months for patients who received chemotherapy (HR, 0.78; 95% CI, 0.63–0.96; P = .0095). Among all patients, the median OS was 7.1 months for patients who received pembrolizumab and 7.1 months for patients who received chemotherapy (HR, 0.89; 95% CI, 0.75–1.05; P = .0560).

The open-label phase II KEYNOTE-181 study (NCT02564263) included 628 patients with advanced or metastatic squamous cell carcinoma (n = 401) or adenocarcinoma (n = 227) of the esophagus that progressed after one prior therapy. Patients were randomly assigned (1:1) to receive either pembrolizumab (200 mg every 3 weeks for up to 2 years) or chemotherapy (investigator’s choice of paclitaxel, docetaxel, or irinotecan). Primary end points were OS in patients with a PD-L1 CPS of 10 or more, OS in patients with squamous cell carcinoma, and OS in all patients (one-sided alpha, 0.9%, 0.8%, and 0.8%, respectively).[51]

Grade 3 to 5 treatment-related adverse events occurred in 18.2% of patients who received pembrolizumab and 40.9% of patients who received chemotherapy.

The open-label phase II KEYNOTE-181 study (NCT02564263) included 628 patients with advanced or metastatic squamous cell carcinoma (n = 401) or adenocarcinoma (n = 227) of the esophagus that progressed after one prior therapy. Patients were randomly assigned (1:1) to receive either pembrolizumab (200 mg every 3 weeks for up to 2 years) or chemotherapy (investigator’s choice of paclitaxel, docetaxel, or irinotecan). Primary end points were OS in patients with a PD-L1 CPS of 10 or more, OS in patients with squamous cell carcinoma, and OS in all patients (one-sided alpha, 0.9%, 0.8%, and 0.8%, respectively).[51]

Patients in this study had not received prior immunotherapy.

The ATTRACTION-3 study (NCT02569242), a multicenter, randomized, open-label, phase III trial, included 419 patients with squamous or adenosquamous esophageal cancer refractory or intolerant to one previous fluoropyrimidine-based and platinum-based chemotherapy. Patients were randomly assigned (1:1) to receive either nivolumab (240 mg every 2 weeks) (n = 210) or investigator's choice of chemotherapy (weekly paclitaxel or docetaxel every 3 weeks) (n = 209). The primary end point was OS.[52]

The ATTRACTION-3 study (NCT02569242), a multicenter, randomized, open-label, phase III trial, included 419 patients with squamous or adenosquamous esophageal cancer refractory or intolerant to one previous fluoropyrimidine-based and platinum-based chemotherapy. Patients were randomly assigned (1:1) to receive either nivolumab (240 mg every 2 weeks) (n = 210) or investigator's choice of chemotherapy (weekly paclitaxel or docetaxel every 3 weeks) (n = 209). The primary end point was OS.[52]

At a follow-up time of 17.6 months, OS was significantly improved in the nivolumab group compared with the chemotherapy group (median OS, 10.9 months [95% CI, 9.2–13.3] vs. 8.4 months [95% CI, 7.2–9.9]) (HRdeath, 0.77; 95% CI, 0.62–0.96; P = .019).[52][Level of evidence A1]

The ATTRACTION-3 study (NCT02569242), a multicenter, randomized, open-label, phase III trial, included 419 patients with squamous or adenosquamous esophageal cancer refractory or intolerant to one previous fluoropyrimidine-based and platinum-based chemotherapy. Patients were randomly assigned (1:1) to receive either nivolumab (240 mg every 2 weeks) (n = 210) or investigator's choice of chemotherapy (weekly paclitaxel or docetaxel every 3 weeks) (n = 209). The primary end point was OS.[52]

Grade 3 or 4 treatment-related adverse events occurred in 38 of 209 patients (18%) in the nivolumab group and 131 of 208 patients (63%) in the chemotherapy group.

The ATTRACTION-3 study (NCT02569242), a multicenter, randomized, open-label, phase III trial, included 419 patients with squamous or adenosquamous esophageal cancer refractory or intolerant to one previous fluoropyrimidine-based and platinum-based chemotherapy. Patients were randomly assigned (1:1) to receive either nivolumab (240 mg every 2 weeks) (n = 210) or investigator's choice of chemotherapy (weekly paclitaxel or docetaxel every 3 weeks) (n = 209). The primary end point was OS.[52]

The most frequent grade 3 or 4 treatment-related adverse events were anemia (4 patients [2%]) in the nivolumab group and decreased neutrophil count (59 patients [28%]) in the chemotherapy group. Five deaths were treatment-related: two in the nivolumab group (one of interstitial lung disease and one of pneumonitis) and three in the chemotherapy group (one of pneumonia, one of spinal cord abscess, and one of interstitial lung disease).