Emerging role of nivolumab in the management of patients with non-small-cell lung cancer: current data and future perspectives

Figures & data

Table 1 Pharmacodynamics and pharmacokinetics of nivolumab

Characteristics	Values
PDL1-binding affinity^Citation88	Kd =2.6 nmol/L
PD1 occupancy^Citation23	85% (mean), 72% (plateau)
Half-life^Citation23	3 mg/kg dose: 12 days 10 mg/kg dose: 20 days
Volume of distribution^Citation89,Citation90	8.04 L
Clearance^Citation89,Citation90	9.50 mL/h

Table 2 Selected trials of nivolumab

Study	Phase	Patients	ORR	Median PFS	Median OS	Grade 3–4 adverse events
Gettinger et al^Citation26	I	129 pretreated squamous and nonsquamous patients	17% (across all doses); 3% (1 mg/kg); 24% (3 mg/kg); 20% (10 mg/kg) >5% PDL1 expression: 15% PDL1-negative: 14%	2.3 months (across all doses) >5% PDL1 expression: 3.3 months PDL1-negative: 1.8 months	9.9 months (across all doses) >5% PDL1 expression: 7.8 months PDL1-negative: 10.5 months	14%
Gettinger et al,^Citation35 Hellmann et al^Citation36	I	52 first-line squamous and nonsquamous patients	23% PDL1-positive ≥50%: 50% PDL1-negative: <14%	3.6 months	1-year OS: 73%	19%
Gettinger et al^Citation40	I	21 first line, EGFR mutant-positive patients; nivolumab + erlotinib	19%	6-month PFS: 51%	NR	24%
Antonia et al^Citation45	I	56 first-line squamous and nonsquamous patients; nivolumab vs platinum doublet	33%–47%	6-month PFS: 38%–71%	13–21 months	45%
Rizvi et al,^Citation39 Hellmann et al^Citation36	I	148 first-line patients; nivolumab + ipilimumab	Nivo 1 mg/kg Q3W + Ipi 1 mg/kg Q3W, followed by Nivo Q2W: 13% Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W: 25% Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W: 39% Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W: 31%	Nivo 1 mg/kg Q3W + Ipi 1 mg/kg Q3W, followed by Nivo Q2W: 10.6 months Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W: 4.9 months Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W: 8 months Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W: 8.3 months	NR	Nivo 1 mg/kg Q3W + Ipi 1 mg/kg Q3W, followed by Nivo Q2W: 29% Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W: 35% Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W: 29% Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W: 28%
Rizvi et al^Citation28	II	117 pretreated squamous patients	14.5%	1.9 months	8.2 months	17%
Brahmer et al^Citation30	III	272 pretreated squamous patients; nivolumab vs docetaxel	20% vs 9% <1% PDL1 expression: 17% vs 10% >10% PDL1 expression: 19% vs 9%	3.5 months vs 2.8 months <1% PDL1 expression: 3.1 vs 3 months >10% PDL1 expression: 3.7 vs 3.3 months	9.2 vs 6.2 months <1% PDL1 expression: 8.7 vs 5.9 months >10% PDL1 expression: 11 vs 7.1 months	7% vs 55%
Borghaei et al^Citation32	III	582 pretreated nonsquamous patients; nivolumab vs docetaxel	19.2% vs 12.4% <1% PDL1 expression: 9% vs 15% >10% PDL1 expression: 37% vs 13%	2.3 vs 4.2 months <1% PDL1 expression: 2.1 vs 3.6 months >10% PDL1 expression: 5 vs 3.7 months	12.2 vs 9.4 months <1% PDL1 expression: 10.5 vs 10.1 months >10% PDL1 expression: 19 vs 8 months	10.5% vs 53.7%
Socinski et al^Citation37	III	423 first-line patients; nivolumab vs investigator-choice chemotherapy	26.1% vs 33.5% (≥5% PDL1 expression)	4.2 vs 5.9 months (≥5% PDL1 expression)	14.4 vs 13.2 months (≥5% PDL1 expression)	18% vs 51%

Abbreviations: ORR, objective response rate; PFS, progression-free survival; OS, overall survival; NR, not reached; Q2W, every 2 weeks; Q3W, every 3 weeks; Q6W, every 6 weeks; Q12W, every 12 weeks.

Table 3 Selected ongoing trials of nivolumab

Study	Phase	Treatment	Patient population	Primary end point
CheckMate 078	III	Nivolumab vs docetaxel	Second line after platinum-based chemotherapy, all histologies	OS
CheckMate 227	III	Nivolumab or nivolumab + ipilimumab or nivolumab + platinum-doublet chemotherapy vs platinum-doublet chemotherapy alone	First line, all histologies	OS
CheckMate 153	III	Nivolumab	Second line, all histologies	Incidence of high-grade (3–5) treatment-related adverse events

Abbreviation: OS, overall survival.

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