Sex difference in response to non-small cell lung cancer immunotherapy: an updated meta-analysis

Figures & data

Figure 1. A schematic flow for the selection of articles included in this meta-analysis.

Table 1. Characteristics of included clinical trials in the meta-analysis.

Author, year	Trial phase	Line	Histotype	Agent of immunotherapy	Number of patients		Therapeutic regimen		Number of inclusions		Median follow-up time
					Male	Female	Treatment	Control	Treatment	Control
Brahmer J et al., 2015	3	Non-first	Sq	PD-1	208	64	Nivolumab	Docetaxel	135	137	11+ months
Borghaei H et al., 2015	3	Non-first	Non-sq	PD-1	319	263	Nivolumab	Docetaxel	292	290	18 months
Carbone DP et al., 2017	3	First	All	PD-1	332	209	Nivolumab	Chemotherapy	271	270	13.5 months
Govindan R et al., 2017	3	First	Sq	CTLA-4	635	114	Ipilimumab + chemotherapy	Placebo + chemotherapy	388	361	12.5 months
Fehrenbacher L et al., 2018	3	Non-first	All	PD-L1	758	467	Atezolizumab	Docetaxel	613	612	21 months
Barlesi F et al., 2018	3	Non-first	All	PD-L1	367	162	Avelumab	Docetaxel	264	265	17.8+ months
Gandhi L et al., 2018	3	First	Non-sq	PD-1	363	253	Pembrolizumab + chemotherapy	Placebo + chemotherapy	410	206	10.5 months
Paz-Ares L et al., 2018	3	First	Sq	PD-1	455	104	Pembrolizumab + chemotherapy	Placebo + chemotherapy	278	281	7.8 months
West H et al., 2019	3	First	Non-sq	PD-L1	400	279	Atezolizumab + chemotherapy	Chemotherapy	451	228	18.5+ months
Reck M et al., 2019	3	First	All	PD-1	187	118	Pembrolizumab	Chemotherapy	154	151	25.2 months
Hellmann MD et al., 2019	3	First	All	PD-1 + CTLA-4	515	278	Nivolumab + ipilimumab	Chemotherapy	396	397	29.3+ months
Herbst RS et al., 2020	2/3	Non-first	All	PD-1	634	399	Pembrolizumab	Docetaxel	690	343	42.6 months
Wu YL et al., 2021	3	First	All	PD-1	224	38	Pembrolizumab	Chemotherapy	128	134	33.0 months
Nishio M et al., 2021	3	First	Non-sq	PD-L1	384	194	Atezolizumab + chemotherapy	Chemotherapy	292	286	14.8 months
Faivre-Finn C et al., 2021	3	Non-first	All	PD-L1	500	213	Durvalumab	Placebo	476	237	34.2 months
Paz-Ares L et al., 2021	3	First	All	PD-1 + CTLA-4	504	215	Nivolumab + ipilimumab +  chemotherapy	Chemotherapy	361	358	13.2 months

sq: squamous; non-sq: non-squamous; PD-1: programmed cell death protein 1; PD-L1: programmed cell death 1 ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated protein 4.

Figure 2. Forest plot of comparison: overall survival of patients receiving ICIs alone or with chemotherapy versus patients not receiving ICIs (receiving chemotherapy or placebo only) (male: p < .001, female: p < .001, overall: p < .001).

Figure 3. Forest plot of comparison based on whether the intervention group contains chemotherapy. (a) Overall survival of patients receiving ICIs plus chemotherapy versus patients receiving chemotherapy alone (male: p < .001, female: p = .018, overall: p < .001). (b) Overall survival of patients receiving ICIs versus patients receiving chemotherapy alone (male: p < .001, female: p = .005, overall: p < .001).

Figure 4. Forest plot of comparison based on treatment stage. (a) Overall survival of patients receiving ICIs with or without chemotherapy versus patients not receiving ICIs (receiving chemotherapy or placebo only) in first line (male: p < .001, female: p = .023, overall: p < .001). (b) Overall survival of patients receiving ICIs with or without chemotherapy versus patients not receiving ICIs (receiving chemotherapy or placebo only) in non-first line (male: p < .001, female: p < .001, overall: p < .001).

Figure 5. Forest plot of comparison based on the type of ICIs. (a) Overall survival of patients receiving PD-1 inhibitor with or without chemotherapy versus patients not receiving ICIs (receiving chemotherapy or placebo only) (male: p < .001, female: p = .006, overall: p < .001). (b) Overall survival of patients receiving PD-L1 inhibitor with or without chemotherapy versus patients not receiving ICIs (receiving chemotherapy or placebo only) (male: p < .001, female: p = .003, overall: p < .001).

Figure 6. Forest plot of comparison based on histological type. (a) Overall survival of patients receiving ICIs with or without chemotherapy versus patients not receiving ICIs (receiving chemotherapy or placebo only) in squamous NSCLC (male: p = .005, female: p = .400, overall: p = .015). (b) Overall survival of patients receiving ICIs with or without chemotherapy versus patients not receiving ICIs (receiving chemotherapy or placebo only) in non-squamous NSCLC (male: p = .005, female: p = .011, overall: p = .001).