Efficacy and safety of nanoparticle albumin-bound paclitaxel in non-small cell lung cancer: a systematic review and meta-analysis

Figures & data

Figure 1. Flowchart showing the selection of study for the meta-analysis.

Table 1. Characteristics of the included comparative studies.

	Study	Year	Stage	Treatment arms	Number	Median age	ORR	95%CI(ORR)	RR(ORR)	PFS	95% CI(PFS)	HR(PFS)	OS	95% CI (OS)	HR(OS)
	Miyako Satouchi[10]	2013	IIIB/IV	100 mg/m2 nab-P weekly + C (under the curve =6), every 3 weeks	74	65	35%	[0.810 , 2.143]	1.318	6.9 months	[0.539 , 1.325]	0.845	16.7 months	[0.608 , 1.425]	0.930
				200 mg/m2 sb-P + C (under the curve =6) every 3 weeks	75	64	27%			5.6 months			15.9 months
	M. A. Socinski[11]	2012	IIIB/IV	100 mg/m2 nab-P weekly + C (under the curve =6), every 3 weeks	447	58	32%	NR	NR	6.0 months	[0.759 , 1.074]	0.903	11.4 months	[0.855 , 1.167]	0.999
				200 mg/m2 sb-P + C (under the curve =6) every 3 weeks	449	59	25%			5.8 months			11.3 months
	M. A. Socinski 1/2[11]	2012	IIIB/IV	100 mg/m2 nab-P weekly + C (under the curve =6), every 3 weeks	74	72	34%	NR	NR	8.0 months	[0.420 , 1.123]	0.687	19.9 months	[0.388 , 0.875]	0.583
				200 mg/m2 sb-P + C (under the curve =6) every 3 weeks	82	72	24%			6.8 months			10.4 months
	Vera Hirsh[12]	2016	IIIB/IV	100 mg/m2 nab-P weekly + C (under the curve =6), every 3 weeks	31	65	52%	[0.976 , 3.837]	1.935	10.months	[0.200 , 0.868]	0.42	17.5 months	[0.298 , 1.026]	0.550
				200 mg/m2 sb-P + C (under the curve =6) every 3 weeks	30	65	27%			4.9 months			11.1 months
	Vera Hirsh 1/2[12]	2016	IIIB/IV	100 mg/m2 nab-P weekly + C (under the curve =6), every 3 weeks	490	59	31%	[1.039 , 1.553]	1.270	6.0months	[0.801 , 1.116]	0.95	11.6 months	[0.817 , 1.101]	0.950
				200 mg/m2 sb-P + C (under the curve =6) every 3 weeks	501	60	25%			5.8months			11.2 months
	Corey J. Lange[13]	2015	IIIB/IV	100 mg/m2 nab-P weekly + C (under the curve =6), every 3 weeks	26	69.5	31%	[0.624 , 4.423]	1.662	6.0 months	[0.269 , 1.370]	0.607	9.7 months	[0.418 , 1.624]	0.824
				200 mg/m2 sb-P + C (under the curve =6) every 3 weeks	27	71	19%			4.7months			9.3 months
	Corey J. Langer 1/1[13]	2015	IIIB/IV	100 mg/m2 nab-P weekly + C (under the curve =6), every 3 weeks	198	61.5	35%	[0.986 , 1.777]	1.324	7.8months	[0.595 , 1.023]	0.780	13.8 months	[0.672 , 1.082]	0.853
				200 mg/m2 sb-P + C (under the curve =6) every 3 weeks	206	64	27%			5.7 months			12.4 months
	Corey J. Langer 1/2[13]	2015	IIIB/IV	100 mg/m2 nab-P weekly + C (under the curve =6), every 3 weeks	289	57	32%	[0.990 , 1.672]	1.287	5.6months	[0.814 , 1.257]	1.012	11.9 months	[0.819 , 1.209]	0.995
				200 mg/m2 sb-P + C (under the curve =6) every 3 weeks	291	57	25%			6.4 months			11.5 months
	Mark A. Socinski[14]	2012	IIIB/IV	100 mg/m2 nab-P weekly + C (under the curve =6), every 3 weeks	521	60	33%	[1.082 , 1.593]	1.313	6.3months	[0.767 , 1.060]	0.902	12.1months	[ 0.797 , 1.066]	0.922
				200 mg/m2 sb-P + C (under the curve =6) every 3 weeks	531	60	25%;			5.8months			11.2months

Nab-P: nab-paclitaxel; sb-P: solvent-based paclitaxel; C: carboplatin; ORR: overall response rate; PFS: progression-free survival; OS: overall survival; RR: rate ratio; HR: hazard ratio; 95% CI: 95% confidence interval; NR: not reported; M. A. Socinski: the age of patients <70 years old; M. A. Socinski ½: the age of patients ≥70 years old; Vera Hirsh: patients were included with Diabetes; Vera Hirsh ½: patients were included without Diabetes; Corey J. Langer: patients were included with moderate renal impairment; Corey J. Langer 1/1: patients were included with mild renal impairment; Corey J. Langer ½: patients were included with normal renal function.

Figure 2. Quality assessment of the included comparative studies. +: low risk of bias; −: high risk of bias; ?: unclear risk of bias.

Figure 3. Overall response rate of (ORR) nab-paclitaxel + carboplatin arm versus that of sb-paclitaxel + carboplatin arm. All studies providing RR for ORR were pooled together and stratified by the median age of patients. The fixed-effects model was used in the analysis.

Figure 4. Overall survival (OS) of nab-paclitaxel + carboplatin arm versus that of sb-paclitaxel + carboplatin arm. All studies providing HR for OS were pooled together and stratified by the median age of patients. The fixed-effects model was used in the analysis.

Figure 5. Progression-free survival (PFS) of nab-paclitaxel + carboplatin arm versus that of sb-paclitaxel + carboplatin arm. All studies providing HR for PFS were pooled together and stratified by the median age of patients. The fixed-effects model was used in the analysis.

Figure 6. Funnel plot analysis of potential publication bias. (a) Rate ratio for overall response rate. (b) Hazard ratios for progression-free survival. (c) Hazard ratios for overall survival.

Table 2. The meta-analysis result of the toxic effects in comparative studies.

Toxic effects	nab-PC	sb-PC	I2(%)	Heterogeneity p	OR(95%CI)	p
Hematologic adverse events
Neutropenia
Grade ≥3	1011/2121	1265/2161	17	>.1	0.65[0.57, 0.73]	<.00001
Anemia
Grade ≥3	582/2121	151/2161	0	>.1	5.04[4.16, 6.10]	<.00001
Thrombocytopenia
Grade ≥3	385/2121	185/2161	0	>.1	2.37[1.97, 2.86]	<.00001
Nonhematologic adverse events
Fatigue
Grade ≥3	130/2127	164/2171	15	>.1	0.80[0.63, 1.01]	.06
Alopecia
Grade ≥3	9/1099	0/1123	0	>.1	7.18[1.29, 39.86]	.02
Nausea
Grade ≥3	16/1613	8/1647	0	>.1	1.90[0.86, 4.21]	.11
Sensory neuropathy
Grade ≥3	47/1613	195/1647	0	>.1	0.22[0.16, 0.31]	<.00001
Arthralgia
Grade ≥3	0/2127	44/2171	0	>.1	0.08[0.03, 0.23]	<.00001
Myalgia
Grade ≥3	16/2127	45/2171	0	>.1	0.39[0.22, 0.67]	.00006
Anorexia
Grade ≥3	41/2055	20/2096	0	>.1	2.06[1.22, 3.50]	.007
Febrile neutropenia
Grade ≥3	24/1541	30/1572	0	>.1	0.82[0.48, 1.40]	.46
Peripheral neuropathy
Grade ≥3	17/514	60/524	0	>.1	0.26[0.15, 0.46]	<.00001

nab-PC: nab-paclitaxel plus carboplatin; sb-PC: solvent-based paclitaxel plus carboplatin; OR: Odds ratio; CI: Confidence interval.

Table 3. Characteristics of the non-comparative studies.

Study	Year	Stage	Treatment arms	Number	Median age	ORR
M. R. Green[15]	2006	IIIB/IV	260 mg/m2 nab-P was administered every 3 weeks	43	58	16.30%
Craig Reynolds[16]	2009	IIIB/IV	300 mg/m2 nab-P, C (area under the curve =6), and bevacizumab 15 mg/kg every 21 days	48	67	31.00%
Pu-Yuan Xing[17]	2013	I	130 mg/m2 nab-P was administered	21	56	28.60%
Ying Fang[18]	2014	IIIB/IV	125 mg/m2 nab-P on day 1 and day 8, cisplatin 75 mg/m2 on day 1,C (area under the curve =5) on day 1	40	61	50.00%
Feng Jin[19]	2016	IIIB/IV	100 mg/m2 nab-P was administered weekly on days 1, 8, and 15, followed by 1 week of rest	42	>65	21.43%
Qi Zheng [20]	2012	NR	100 mg/m2 nab-P was administered weekly on days 1, 8, and 15, followed by 1 week of rest	20	66	30.00%
Mitsunori Higuchi[21]	2017	IIIB/IV	70-100mg/m2 nab-P was administered on days 1, 8 and 15, with C (under the curve of 4–6) every 4 week.	25	66	32.00%
Eisaku Miyauchi[22]	2017	IV	75mg/m2 nab-P was administered on days 1, 8, and 15 every 4 weeks combined with C (under the curve =6 )on day 1	32	78	50.00%

P: nab-paclitaxel; C: carboplatin.

Table 4. The Summaries of the major serious adverse events in non-comparative studies.

Study	Leukopenia	Neutropenia	Anemia	Fatigue	Anorexia	Thrombocytopenia
M. R. Green[15]	0	9	0	7	NR	0
Craig Reynolds[16]	2	26	NR	8	2	5
Pu-Yuan Xing[17]	NR	2	NR	1	NR	NR
Ying Fang[18]	10	3	NR	NR	NR	4
Feng Jin[19]	2	1	0	4	NR	0
Qi Zheng[20]	4	4	0	3	0	0
Mitsunori Higuchi[21]	7	0	2	NR	NR	3
Eisaku Miyauchi[22]	12	15	11	2	3	8
Events, n(%)	37(14.8%)	60(22.1%)	13(8.0%)	25(12.1%)	5(5%)	20(8%)
Total, n	250	271	162	206	100	250

Abbreviations: NR, not reported.

Table 5. The Study designs and MINORS appraisal scores for the non-comparative studies.

MINORS	methodological	criteria
Study	study design	1	2	3	4	5	6	7	8	Total
M. R. Green, 2006[15]	non-comparative	2	1	2	1	2	1	1	2	12
Craig Reynolds, 2009[16]	non-comparative	2	1	2	1	2	2	1	1	12
Pu-Yuan Xing, 2013[17]	non-comparative	2	2	2	1	2	2	2	2	15
Ying Fang, 2014[18]	non-comparative	2	2	2	2	2	2	2	1	15
Feng Jin, 2016[19]	non-comparative	2	1	2	1	2	2	2	2	14
Qi Zheng, 2012[20]	non-comparative	2	1	2	1	2	2	2	2	14
Mitsunori,2017[21]	non-comparative	2	0	2	1	2	1	2	1	11
Eisaku, 2017[22]	non-comparative	2	1	2	1	2	2	2	2	14

The MINORS criteria include the following items:(1) a clearly stated aim; (2) inclusion of consecutive patients; (3) prospective data collection; (4) endpoints appropriate to the aim of the study; (5) unbiased assessment of the study endpoint; (6) a follow-up period appropriate to the aims of the study; (7) Loss to follow up less than 5%; (8) Prospective calculation of the study size.

The items are scored as follows: 0 (not reported); 1 (reported but inadequate); or 2 (reported and adequate). The ideal global score would be 16 for the non-comparative studies.

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