Pembrolizumab

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population.

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population.

At the second interim analysis, pembrolizumab alone showed improved or noninferior OS compared with cetuximab with chemotherapy. The median OS results were reported as follows:[7][Level of evidence A1]

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population. › At the second interim analysis, pembrolizumab alone showed improved or noninferior OS compared with cetuximab with chemotherapy. The median OS results were reported as follows:[7][Level of evidence A1]

Among the population with a CPS of 20 or higher, the median OS was 14.9 months in patients who received pembrolizumab alone and 10.7 months in patients who received cetuximab with chemotherapy (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.45–0.83; P = .0007).

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population. › At the second interim analysis, pembrolizumab alone showed improved or noninferior OS compared with cetuximab with chemotherapy. The median OS results were reported as follows:[7][Level of evidence A1]

Among the population with a CPS of 1 or higher, the median OS was 12.3 months in patients who received pembrolizumab alone and 10.3 months in patients who received cetuximab with chemotherapy (HR, 0.78; 95% CI, 0.64–0.96; P = .0086).

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population. › At the second interim analysis, pembrolizumab alone showed improved or noninferior OS compared with cetuximab with chemotherapy. The median OS results were reported as follows:[7][Level of evidence A1]

Among the total population, patients who received pembrolizumab alone had noninferior OS (11.6 months) compared with patients who received cetuximab with chemotherapy (10.7 months) (HR, 0.85; 95% CI, 0.71–1.03; P = .0456).

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population.

Pembrolizumab with chemotherapy showed improved OS versus cetuximab with chemotherapy. The OS results were reported as follows:

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population. › Pembrolizumab with chemotherapy showed improved OS versus cetuximab with chemotherapy. The OS results were reported as follows:

At the second interim analysis, among the total population, the median OS was 13.0 months in patients who received pembrolizumab with chemotherapy and 10.7 months in patients who received cetuximab with chemotherapy (HR, 0.77; 95% CI, 0.63–0.93; P = .0034).

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population. › Pembrolizumab with chemotherapy showed improved OS versus cetuximab with chemotherapy. The OS results were reported as follows:

At the final analysis, among the population with a CPS of 20 or higher, the median OS was 14.7 months in patients who received pembrolizumab with chemotherapy and 11.0 months in patients who received cetuximab with chemotherapy (HR, 0.60; 95% CI, 0.45–0.82; P = .0004).

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population. › Pembrolizumab with chemotherapy showed improved OS versus cetuximab with chemotherapy. The OS results were reported as follows:

At the final analysis, among the population with a CPS of 1 or higher, the median OS was 13.6 months in patients who received pembrolizumab with chemotherapy and 10.4 months in patients who received cetuximab with chemotherapy (HR, 0.65; 95% CI, 0.53–0.80; P < .0001).

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population.

At the second interim analysis, neither pembrolizumab alone nor pembrolizumab with chemotherapy improved PFS.

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population.

At the final analysis, grade 3 or higher all-cause adverse events occurred in 164 of 300 patients (55%) in the pembrolizumab-alone group, 235 of 276 patients (85%) who received pembrolizumab with chemotherapy, and 239 of 287 patients (83%) who received cetuximab with chemotherapy.

KEYNOTE-048 (NCT02358031) was a nonblinded, randomized, phase III study of participants with untreated locally incurable metastatic or recurrent head and neck SCC that was performed at 200 sites in 37 countries.[7] A total of 882 patients were randomly assigned in a 1:1:1 ratio to receive pembrolizumab alone (n = 301), pembrolizumab plus a platinum and fluorouracil (5-FU) (pembrolizumab with chemotherapy) (n = 281), or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy) (n = 300). Investigators, patients, and representatives of the sponsor were masked to the programmed death-ligand 1 (PD-L1) combined positive score (CPS) results; PD-L1 positivity was not required for study entry. A total of 754 patients (85%) had a CPS of 1 or higher and 381 patients (43%) had a CPS of 20 or higher.The primary end points were overall survival (OS) and progression-free survival (PFS). Progression was defined as radiographically confirmed disease progression or death from any cause, whichever came first, in the intention-to-treat population.

Adverse events led to death in 25 patients (8%) in the pembrolizumab-alone group, 32 patients (12%) who received pembrolizumab with chemotherapy, and 28 patients (10%) who received cetuximab with chemotherapy.

The phase III KEYNOTE-040 (NCT02252042) trial included patients with incurable metastatic or recurrent head and neck SCC who had received platinum-based treatment within 3 to 6 months.[5] Patients were randomly assigned to the pembrolizumab arm (200 mg every 3 weeks [247 patients]) or to the standard therapy arm of the investigator’s choice (methotrexate, docetaxel, or cetuximab [248 patients]). Patients received treatment until progression or toxicity. The maximum duration of pembrolizumab was 24 months. The primary end point was OS in the intention-to-treat population.

The phase III KEYNOTE-040 (NCT02252042) trial included patients with incurable metastatic or recurrent head and neck SCC who had received platinum-based treatment within 3 to 6 months.[5] Patients were randomly assigned to the pembrolizumab arm (200 mg every 3 weeks [247 patients]) or to the standard therapy arm of the investigator’s choice (methotrexate, docetaxel, or cetuximab [248 patients]). Patients received treatment until progression or toxicity. The maximum duration of pembrolizumab was 24 months. The primary end point was OS in the intention-to-treat population.

The median OS was 8.4 months in the pembrolizumab arm and 6.9 months in the standard therapy arm (HR, 0.80; 95% CI, 0.65–0.98; nominal P = .0161).[5][Level of evidence A1]

The phase III KEYNOTE-040 (NCT02252042) trial included patients with incurable metastatic or recurrent head and neck SCC who had received platinum-based treatment within 3 to 6 months.[5] Patients were randomly assigned to the pembrolizumab arm (200 mg every 3 weeks [247 patients]) or to the standard therapy arm of the investigator’s choice (methotrexate, docetaxel, or cetuximab [248 patients]). Patients received treatment until progression or toxicity. The maximum duration of pembrolizumab was 24 months. The primary end point was OS in the intention-to-treat population.

Pembrolizumab was associated with fewer grade 3 or higher adverse events (pembrolizumab, 13% vs. standard therapy, 36%). The most common treatment-related adverse events were hypothyroidism (13%) in the pembrolizumab arm and fatigue (18%) in the standard therapy arm.

The phase III KEYNOTE-040 (NCT02252042) trial included patients with incurable metastatic or recurrent head and neck SCC who had received platinum-based treatment within 3 to 6 months.[5] Patients were randomly assigned to the pembrolizumab arm (200 mg every 3 weeks [247 patients]) or to the standard therapy arm of the investigator’s choice (methotrexate, docetaxel, or cetuximab [248 patients]). Patients received treatment until progression or toxicity. The maximum duration of pembrolizumab was 24 months. The primary end point was OS in the intention-to-treat population.

In patients who received pembrolizumab, there were four treatment-related deaths resulting from large intestinal perforation, Stevens-Johnson syndrome, and unspecified malignant progression. Two treatment-related deaths in the standard therapy arm resulted from malignant progression and pneumonia.

The phase III KEYNOTE-040 (NCT02252042) trial included patients with incurable metastatic or recurrent head and neck SCC who had received platinum-based treatment within 3 to 6 months.[5] Patients were randomly assigned to the pembrolizumab arm (200 mg every 3 weeks [247 patients]) or to the standard therapy arm of the investigator’s choice (methotrexate, docetaxel, or cetuximab [248 patients]). Patients received treatment until progression or toxicity. The maximum duration of pembrolizumab was 24 months. The primary end point was OS in the intention-to-treat population.

The PD-L1 CPS was 1 or higher in 79% of the patients in the pembrolizumab arm and 77% of the patients in the standard therapy arm.

The phase III KEYNOTE-040 (NCT02252042) trial included patients with incurable metastatic or recurrent head and neck SCC who had received platinum-based treatment within 3 to 6 months.[5] Patients were randomly assigned to the pembrolizumab arm (200 mg every 3 weeks [247 patients]) or to the standard therapy arm of the investigator’s choice (methotrexate, docetaxel, or cetuximab [248 patients]). Patients received treatment until progression or toxicity. The maximum duration of pembrolizumab was 24 months. The primary end point was OS in the intention-to-treat population.

Compared with patients treated with standard therapy, a reduced HRdeath was noted for patients who received pembrolizumab and had PD-1 expression on their tumors or in the tumor microenvironment as noted by a PD-L1 CPS of 1 or higher (HR, 0.74; 95% CI, 0.58–0.93; nominal P = .0049) or a PD-L1 tumor proportion score of 50% or higher (HR, 0.53; 95% CI, 0.35–0.81; nominal P = .0014).