Efficacy and safety of programmed death 1 inhibitors in patients with advanced non-small cell lung cancer: a meta-analysis

Figures & data

Figure 1 Flow diagram of the literature search and trial selection process.

Table 1 Characteristics of the included studies

Study	Year	Design	N	Histology	Trial	Control	Outcomes
Horn et al.^Citation13	2017	International, randomized, open-label, phase III studies	272	Squamous NSCLC	Nivolumab(3 mg/kg every 2 weeks)	Docetaxel(75 mg/m^2 every 3 weeks)	OS 、PFS ORR、AEs、
Horn et al.^Citation13	2017	International, randomized, open-label, phase III studies	582	Nonsquamous NSCLC	Nivolumab(3 mg/kg every 2 weeks)	Docetaxel(75 mg/m^2 every 3 weeks)	OS 、PFS ORR、AEs、
Carbone et al.^Citation14	2017	International, randomized, open-label, phase III trial	541	Squamous-cell or nonsquamous stage IV or recurrent NSCLC	Nivolumab(3 mg/kg every 2 weeks)	Platinum-based chemotherapy (every 3 weeks for four to six cycles)	OS 、PFS 、ORR、AEs、
Herbst et al.^Citation16	2016	Randomized, open-label, phase Ⅱ/III study	687	Squamous、Adenocarcinoma NSCLC	Pembrolizumab (2 mg/kg every 3 weeks.)	Docetaxel 75 mg/m^2 every 3 weeks.	OS 、ORR、AEs、
Herbst et al.^Citation16	2016	Randomized, open-label, phase Ⅱ/III study	689	Squamou、Adenocarcinom NSCLC	Pembrolizumab (10 mg/kg every 3 weeks)	Docetaxel 75 mg/m^2 every 3 weeks.	OS、 OR、AEs、
Reck et al.^Citation15	2016	Open-label, phase III trial	305	Squamous、Nonsquamous NSCLC	Pembrolizumab (at a fixed dose of 200 mg every 3 weeks)	Platinum-based chemotherapy	OS 、PFS ORR、AEs
Borghaei et al.^Citation17	2015	Randomized, open-label, international phase III study	582	Nonsquamous NSCLC	Nivolumab (3 mg/kg every 2 weeks)	Docetaxel(75 mg/m^2 every 3 weeks)	OS 、PFS ORR、AEs、
Brahmer et al.^Citation18	2015	Randomized, open-label, international, phase III study	272	Squamous-cell NSCLC	Nivolumab (3 mg/kg every 2 weeks)	Docetaxel(75 mg/m^2 every 3 weeks)	OS 、PFS ORR、AEs、

Abbreviations: OS, overall survival; PFS, progression-free survival; ORR, objective response rate; AEs, adverse events; NSCLC, non-small cell lung cancer.

Table 2 Quality assessment by the Cochrane Collaboration’s tool

Reference	Random Sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias
Horn, L. 2017^Citation13	High risk	Unclear risk	Unclear risk	Unclear risk	Unclear risk	Unclear risk	Unclear risk
Carbone, D.P. 2017^Citation14	Unclear risk	Unclear risk	Unclear risk	Low risk	Low risk	Unclear risk	Unclear risk
Reck, M. 2016^Citation15	Low risk	Unclear risk	Unclear risk	Low risk	Low risk	Unclear risk	Unclear risk
Herbst, R. S. 2016^Citation16	Unclear risk	Unclear risk	High risk	High risk	High risk	Unclear risk	Unclear risk
Borghaei, H. 2015^Citation17	Unclear risk	Unclear risk	High risk	High risk	High risk	Unclear risk	Unclear risk
Brahmer, J. 2015^Citation18	Unclear risk	Unclear risk	High risk	High risk	High risk	Unclear risk	Unclear risk

Figure 2 Forest plots of overall survival for PD-1 inhibitors monotherapy or chemotherapy.

Abbreviations: OS, overall survival; HR, hazard ratio.

Figure 3 Subgroup hazard ratio of progression-free survival for PD-1 inhibitors monotherapy or chemotherapy.

Abbreviations: PFS, progressive-free survival; HR, hazard ratio.

Figure 4 Forest plots of objective response rate for PD-1 inhibitors monotherapy or chemotherapy.

Abbreviations: ORR, objective response rate; RR, risk ratio.

Figure 5 Forest plots of overall survival (OS) for PD-L1 expression level.

Abbreviation: HR, hazard ratio.

Figure 6 Forest plots of relative risks of treatment-related adverse events associated with PD1 versus chemotherapy.

Abbreviations: AEs, adverse events; RR, risk ratio.

Figure 7 Subgroup risk ratio of severe adverse events. (A) Subgroup risk ratio of severe adverse events based on docetaxel and platinum duplexes. (B) Subgroup risk ratio of severe adverse events associated with PD1 versus chemotherapy.

Abbreviations: SAEs, severe adverse events; RR, risk ratio.

Horn L, Spigel DR, Vokes EE, et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, Phase III trials (CheckMate 017 and CheckMate 057). J Clin Res Oncol. 2017;35(35):3924-+. doi:10.1200/JCO.2017.74.3062

 Google Scholar

Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet (London, England). 2016;387(10027):1540‐1550. doi:10.1016/S0140-6736(15)01281-7

 PubMed Web of Science ®Google Scholar

Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–1833. doi:10.1056/NEJMoa160677427718847

 PubMed Web of Science ®Google Scholar

Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–1639. doi:10.1056/NEJMoa150764326412456

 PubMed Web of Science ®Google Scholar

Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–135. doi:10.1056/NEJMoa150462726028407

 PubMed Web of Science ®Google Scholar

Carbone DP, Reck M, Paz-Ares L, et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017;376(25):2415–2426. doi:10.1056/NEJMoa161349328636851

 PubMed Web of Science ®Google Scholar