Potential role of immunotherapy in advanced non-small-cell lung cancer

Figures & data

Figure 1 Immunoediting mechanism.

Notes: Immunoediting occurs in three phases: elimination, equilibrium, and escape. Elimination is a phase in which both innate and adaptive immunities are successful in eliminating tumor cells before clinical investigation is even possible. Equilibrium is when tumor cells survive the elimination phase but keep coexisting with their host while being strictly controlled by immune defenses. Escape is when tumor cells gain the ability to circumvent immune responses and emerge as progressively growing, visible tumors.
Abbreviations: DC, dendritic cell; M0, macrophage; NK, natural killer cell; T_reg, regulatory T-cell; MDSC, myeloid-derived suppressor cell.

Figure 2 Mechanism of action of immune checkpoint inhibitors.

Notes: T_regs depend on the activity of CTLA-4, PD-1, and PD-L1 to induce immunosuppression. Ipilimumab and tremelimumab are monoclonal antibodies that inhibit CTLA-4, while nivolumab, pembrolizumab, atezolizumab, and durvalumab inhibit PD-1 and PD-L1. These drugs act by reducing immuno checkpoint activity on a T_reg-rich microenvironment, thus diminishing tumor evasion.
Abbreviations: T_regs, regulatory T-cells; TCR, T-cell receptor; MHC, major histocompatibility complex.

Table 1 Efficacy and safety of immunotherapies for NSCLC

Immunotherapy	Phase	N	Primary end point	Results
Nivolumab	II^Citation35	202	Efficacy	At 1 year, OS was longer with nivolumab than with docetaxel
	II^Citation38	129	Safety	Serious AEs occurred in 59% of patients
Pembrolizumab	II/III^Citation44	1,034	Efficacy	OS was longer with pembrolizumab (10 mg/kg) than with pembrolizumab (2 mg/kg) or docetaxel (12.7 versus 10.4 versus 8.5 months)
	I^Citation42	495	Safety	Fatigue, pruritus, and decreased appetite are the most common AEs
Atezolizumab	II^Citation47	144	Efficacy	OS was longer with atezolizumab than with docetaxel (12.6 versus 9.7 months)
	I^Citation45	64	Safety	No dose-limiting toxicities were reported, and there were no cases of grade ≥3 pneumonitis
Ipilimumab	II^Citation36	204	Efficacy	irPFS was longer in the paclitaxel and carboplatin plus ipilimumab group than in the paclitaxel and carboplatin plus placebo group (5.6 versus 4.6 months)
			Safety	irAEs were more frequent in the ipilimumab group arms (19% in the concurrent arm versus 15% in the phased arm versus 6% in the placebo)
Tremelimumab	II^Citation32	87	Efficacy	At 3 months, the PFS was longer with tremelimumab than with best supportive care (20% versus 14.3%, respectively)
			Safety	Only the tremelimumab group (20.5%) experienced grade 3/4 AEs, mainly diarrhea and colitis

Abbreviations: NSCLC, non-small-cell lung cancer; OS, overall survival; AEs, adverse effects; irPFS, immune-related PFS; irAEs, immune-related AEs; PFS, progression-free survival.

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