PMC

Kaplan-Meier curves of (A) investigator-assessed progression-free survival (PFS) and (B) overall survival (OS) in all enrolled patients by treatment group: nivolumab 3 mg/kg (NIVO3), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1 + IPI3), and NIVO3 plus ipilimumab 1 mg/kg (NIVO3 + IPI1). Hash marks indicate censored observations.

Response characteristics in all responders by (A) investigator assessment and (B) blinded independent central review assessment. IPI1, ipilimumab 1 mg/kg; IPI3, ipilimumab 3 mg/kg; MSI, microsatellite instability; MSI-H, microsatellite instability–high; NIVO1, nivolumab 1 mg/kg; NIVO3 nivolumab 3 mg/kg; PDL, programmed death ligand; PD-L1+, programmed death-ligand 1–positive; PD-L1−, programmed death-ligand 1–negative.

Kaplan-Meier curves of progression-free survival (PFS) in patients treated with nivolumab 3 mg/kg (NIVO3), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1 + IPI3), and NIVO3 plus ipilimumab 1 mg/kg (NIVO3 + IPI1) per blinded independent central review. All data are based on the November 2016 database cutoff, except for the blinded independent central review data for the NIVO3 group, which are based on the March 2016 database cutoff.

CONSORT diagram for study design and patient disposition. (*) Increased ALT/AST (n = 1 patient) and pneumonitis (n = 1 patient). (†) Increased ALT/AST (n = 3 patients); colitis (n = 2 patients); diarrhea (n = 2 patients); colitis, cystitis, and transaminitis (n = 1 patient); and diarrhea and hyperthyroidism (n = 1 patient). (‡) Acute renal failure, autoimmune hepatitis, diarrhea, enteritis, increased ALT/AST, lymphocytic myocarditis, and pneumonitis (n = 1 patient each). AE, adverse event; IPI1, ipilimumab 1 mg/kg; IPI3, ipilimumab 3 mg/kg; NIVO1, nivolumab 1 mg/kg; NIVO3, nivolumab 3 mg/kg.

Changes from baseline in target lesions over time per blinded independent central review assessment in patients treated with (A) nivolumab 3 mg/kg monotherapy, (B) nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, or (C) nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. All data are based on the November 2016 database cutoff, except for the blinded independent central review data for the nivolumab 3 mg/kg group, which are based on the March 2016 database cutoff. The + signs indicate the occurrence of a new lesion, closed circles indicate off treatment, open squares represent percentage changes from baseline truncated at 100%, and red triangles indicate investigator-assessed confirmed complete or partial responses.

Waterfall plot showing maximum percentage change from baseline in size of tumors in patients treated with nivolumab 3 mg/kg (NIVO3), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1 + IPI3), and NIVO3 plus ipilimumab 1 mg/kg (NIVO3 + IPI1) per blinded independent central review. All data are based on the November 2016 database cutoff, except for the blinded independent central review data for the NIVO3 group, which are based on the March 2016 database cutoff. Patients with 0% best reduction in target lesion are not shown on the plot (NIVO1 + IPI3; n = 1). (*) Indicates patients with a confirmed response. Bars representing patients with a percentage change in tumor burden that exceeded 100% have been truncated.

Changes in tumor burden per investigator assessment in individual patients. Percentage change from baseline in target lesions over time with (A) nivolumab 3 mg/kg (NIVO3), (B) nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1 + IPI3), (C) NIVO3 plus ipilimumab 1 mg/kg (NIVO3 + IPI1), and (D) the reduction in maximum percentage change from baseline in size of tumors by treatment group. Patients with 0% best reduction in target lesion are not shown on the plot (NIVO3, n = 2; NIVO1 + IPI3, n = 1; NIVO3 + IPI1, n = 1). Triangle indicates investigator-assessed confirmed complete or partial response, square indicates percent change truncated at 100%, closed circle represents patients off treatment, and cross represents first occurrence of a new lesion. (*) Indicates patients with a confirmed response (complete or partial response), and the bars representing patients with a percentage change in tumor burden that exceeds 100% have been truncated.