Keynote 189 trial#
Keynote 189 plus#

Keynote 189 plus#

Fifty-six patients (13.7%) allocated to pembrolizumab plus pemetrexed–platinum had completed 35 cycles of pembrolizumab treatment. At data cut-off, 75 patients (18.3%) in the pembrolizumab plus pemetrexed–platinum group and 11 patients (5.3%) in the placebo plus pemetrexed–platinum group were alive and had discontinued or completed study treatment without subsequent treatment. Median duration of treatment was 7.2 months (range, 1 day-35.4 months) in the pembrolizumab plus pemetrexed–platinum group and 4.2 months (range, 1 day-27.2 months) in the placebo plus pemetrexed–platinum group. Seventeen patients in the pembrolizumab plus pemetrexed–platinum group and one patient in the placebo plus pemetrexed–platinum group were continuing to receive pemetrexed. AssessmentsĪt the time of data cut-off (), median time from randomization to data cut-off was 31.0 (range, 26.5-38.8) months, and median time from randomization to death/data cut-off was 18.8 (range, 0.2-38.8) months.

Keynote 189 trial#

Patients in the pembrolizumab group who stopped treatment after attaining an investigator-determined confirmed complete response (CR) as per RECIST v1.1 or those who completed 35 cycles of pembrolizumab with best overall response of stable disease (SD), partial response (PR), or CR, and experienced subsequent disease progression (by blinded independent central review) and had not received new anticancer treatment after the last dose of trial treatment, could receive a second course of pembrolizumab monotherapy for up to 17 cycles if all eligibility criteria related to safety were met. Patients in the placebo plus pemetrexed–platinum group who experienced disease progression confirmed by blinded independent central review using RECIST v1.1 could cross over to receive pembrolizumab monotherapy for up to 35 cycles if safety criteria were met and the patient had no new/progressing brain metastases, had not received any systemic anticancer therapies other than the allocated chemotherapies, and had completed palliative radiotherapy (≤30 Gy) ≥7 days before the first dose of crossover treatment.

Treatment continued until documented disease progression, unacceptable adverse events (AEs), intercurrent illness preventing further treatment administration, investigator decision, or withdrawal of patient consent. Randomization was stratified by PD-L1 tumor proportion score (TPS ≥1% versus <1%), choice of platinum chemotherapy (cisplatin versus carboplatin), and smoking status (never versus former/current).

min/ml for the first four cycles, followed by pemetrexed maintenance therapy until progression or unacceptable toxicity.Patients were randomized 2 : 1 to receive pembrolizumab 200 mg or saline placebo, both administered intravenously every 3 weeks, for up to 35 cycles all patients received pemetrexed 500 mg/m 2 and investigator’s choice of either cisplatin 75 mg/m 2 or carboplatin area under the curve 5 mg Patients provided written informed consent. Study procedures were approved by an institutional review board/ethics committee at each institution. Patients were excluded if they had known active brain metastases and/or carcinomatous meningitis, had active autoimmune disease that required systemic treatment in the last 2 years, had a history of noninfectious pneumonitis that required steroids or current pneumonitis, had received radiation therapy >30 Gy to the lung within 6 months of the first dose of trial treatment, or were receiving systemic immunosuppressive treatment. Patients with clinically stable previously treated brain metastases and with asymptomatic untreated brain metastases ≤1.5 cm were eligible. Briefly, eligible patients were ≥18 years of age, with previously untreated histologically/cytologically confirmed stage IV nonsquamous NSCLC, without EGFR/ ALK aberrations, Eastern Cooperative Oncology Group (ECOG) performance status of 0/1, measurable disease as per RECIST v1.1, and provided a tumor sample for PD-L1 evaluation.