Immune checkpoint inhibitors of the PD-1/PD-L1-axis in non-small cell lung cancer: promise, controversies and ambiguities in the novel treatment paradigm

Figures & data

Table 1. Summary of the 4 most commonly used immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC).

Molecular target of ICI	PD-1 inhibitors		PD-L1 inhibitors
Generic name	Pembrolizumab	Nivolumab	Durvalumab	Atezolizumab
Trade name	Keytruda	Opdivo	Imfinzi	Tecentriq
mAbs used to assess TPS	SP263 & 22C3	SP263 & 28-8	SP263	SP142
PD-L1 cells scored by ICH	TC	TC	TC	TC and/or IC
Approval for 1st line	Monotherapy: advanced, expressing PD-L1 with tumor proportion score (TPS) ≥50% with no EGFR or ALK genomic tumor aberrations Combination therapy: in metastatic squamous and non-squamous provided no EGFR or ALK genomic tumor aberrations	Not approved	Locally advanced Stage III; tumor expressing PD-L1 TPS ≥1% without progression after chemoradiotherapy	Monotherapy: not approved Combination therapy: All allowed in combination with various chemotherapies for metastatic non-squamous; not EGFR mutant or ALK positive
Approval for 2nd line	Monotherapy: metastatic, expressing PD-L1 TPS ≥ 1%; Patients with EGFR or ALK genomic tumor aberrations should first have had disease progression on approved therapy for these aberrations	Monotherapy: locally advanced or metastatic	Not approved	Monotherapy: locally advanced or metastatic; Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before Combination therapy: not mentioned
TPS required for 1st line therapy	≥50% for monotherapy, not required for combination with chemotherapy	Not approved	≥1%	Not approved
TPS required for 2nd line therapy	≥1%	None required	Not approved	None required
TPS investigated in trials	TC ≥1% and ≥50%	TC ≥1%, ≥5% and ≥10%	35% were TC ≥ 25%, 32% TPS 1–24% and 33% TC < 1%.	TC ≥50%; IC ≥10% TC or IC ≥ 5% TC or IC ≥ 1% TC and IC < 1%
Assay antibody clone	22C3	28-8	SP263	SP142
Test platform	Dako Autostainer Link 48		Ventana Benchmark Ultra

mAbs: monoclonal antibody; TPS: tumor proportion score; ICH: immune cytohistochemistry; TC: tumor cells; IC: immune cells.

NB. Approval descriptions based on EMA approvals. The exact approval can vary between the EU (EMA) and USA (FDA).

Table 2. Side-effects from monotherapy with immune checkpoint inhibitors (ICI) of PD-1 vs. PD-L1 in NSCLC.

	ICI of PD-1 (n = 3284) (%)	ICI of PD-L1 (n = 2460) (%)	p Value
Objective response	19	19	.17
All AE	64	66	.8
Grade 3–5 toxicity	13	21	.15
Fatigue	19	21	.4
irAE	16	11	.07
Hypothyroidism (all grades)	6.7	4.2	.07
Pneumonitis (all grades)	4	2	.01

Grade 5 = death; AE: adverse event; irAE: immune-related AE [26].

Table 3. Monthly treatment costs and cost-effectiveness of ICIs for NSCLC, Sweden 2019.

Treatment	Treatment cost (SEK, per month)	QALY gain	ICER (SEK/QALY)	Source
Atezolizumab	63,000	0.52	880,000	[73]
Durvalumab	96,000	1.09	857,440	[67]
Nivolumab	62,000	0.6	890,136	[74]
Pembrolizumab	66,320	1.15	745,585	[72]

QALY: quality-adjusted life-year; ICER: incremental cost-effectiveness ratio.

Pillai RN, Behera M, Owonikoko TK, et al. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature. Cancer. 2018;124(2):271–277.

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