LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD

Figures & data

Figure 1 The LANTERN study design.

Figure 2 LANTERN trial profile.

Note: Data are shown as n (%).
Abbreviation: SFC, salmeterol/fluticasone.

Table 1 Demographics and baseline patient characteristics

Patient characteristics	QVA149 110/50 µg od n=372	SFC 50/500 µg bid n=369
Age, years	64.8 (7.8)	65.3 (7.9)
Sex, male, n (%)	341 (91.7)	331 (89.7)
Race, n (%)
Caucasian	55 (14.8)	58 (15.7)
Asian	314 (84.4)	309 (83.7)
Other	3 (0.8)	2 (0.5)
Duration of COPD, years	5.2 (4.9)	5.1 (4.7)
COPD severity, n (%)a
Mild	2 (0.5)	1 (0.3)
Moderate	192 (51.6)	195 (52.8)
Severe	175 (47.0)	169 (45.8)
GOLD 2014 groups
GOLD B	193 (51.9)	196 (53.1)
GOLD D	176 (47.3)	169 (45.8)
Patients with prior COPD-related medication, n (%)	268 (72.0)	280 (75.9)
ICS users at baseline, n (%)	206 (55.4)	200 (54.2)
Current smokers, n (%)	96 (25.8)	96 (26.0)
COPD exacerbation history, n (%)
0	311 (83.6)	276 (74.8)
1	60 (16.1)	93 (25.2)
≥2	1 (0.3)	0
Postbronchodilator FEV1, L	1.336 (0.392)	1.341 (0.418)
Postbronchodilator FEV1, % predicted	51.6 (12.8)	52.0 (12.9)
Postbronchodilator FEV1, reversibility, %	25.3 (16.9)	22.8 (16.7)
Postbronchodilator FEV1, FVC, %	42.7 (9.9)	43.0 (10.0)
CAT score	13.7 (5.94)	13.8 (6.78)
CAT score category
0–10 (mild)	119 (32.0)	137 (37.1)
11–20 (moderate)	198 (53.2)	155 (42.0)
21–30 (severe)	52 (14.0)	70 (19.0)
31–40 (very severe)	0	2 (0.5)
Missing	3 (0.8)	5 (1.4)
BDI focal score	6.3 (1.79)	6.4 (1.89)
SGRQ total score	39.25 (15.40)	38.81 (15.49)
mMRC grade
2	331 (89.0)	325 (88.1)
3	35 (9.4)	40 (10.8)
4	6 (1.6)	4 (1.1)

Notes: Data are the mean ± standard deviation, unless otherwise stated;

a COPD severity is based on GOLD 2010 criteria.

Abbreviations: od, once daily; bid, twice daily; SFC, salmeterol/fluticasone; GOLD, Global initiative for chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; CAT, COPD assessment test; BDI, baseline dyspnea index; SGRQ, St George’s Respiratory Questionnaire; mMRC, modified Medical Research Council.

Table 2 Primary and secondary efficacy outcomes in the LANTERN study (full analysis set)

Parameters	Day 1			Week 12			Week 26
	QVA149 110/50 µg od	SFC 50/500 µg bid	Treatment difference	QVA149 110/50 µg od	SFC 50/500 µg bid	Treatment difference	QVA149 110/50 µg od	SFC 50/500 µg bid	Treatment difference
Trough FEV1, L	1.26 (0.014)	1.22 (0.013)	0.043 (0.018, 0.067)***	1.28 (0.016)	1.21 (0.016)	0.078 (0.046, 0.111)***	1.26 (0.017)	1.18 (0.017)	0.075 (0.044, 0.107)***
FEV1 AUC0–4h, L	1.32 (0.0096)	1.25 (0.009)	0.065 (0.048, 0.083)***	1.39 (0.016)	1.26 (0.016)	0.125 (0.095, 0.156)***	1.35 (0.017)	1.23 (0.017)	0.122 (0.090, 0.154)***
Peak FEV1, 5 minutes-4 hours, L	1.39 (0.010)	1.33 (0.010)	0.061 (0.041, 0.080)***	1.45 (0.017)	1.33 (0.017)	0.128 (0.096, 0.159)***	1.42 (0.017)	1.30 (0.017)	0.121 (0.088, 0.155)***
Trough FVC, L	3.04 (0.029)	2.96 (0.028)	0.083 (0.037, 0.130)***	3.04 (0.030)	2.84 (0.030)	0.201 (0.146, 0.255)***	2.97 (0.033)	2.79 (0.033)	0.173 (0.115, 0.231)***
Peak FVC, 5 minutes-4 hours, L	3.27 (0.022)	3.19 (0.022)	0.084 (0.044, 0.124)***	3.31 (0.031)	3.10 (0.030)	0.207 (0.152, 0.262)***	3.25 (0.033)	3.07 (0.033)	0.176 (0.116, 0.236)***
TDI focal score	–	–	–	2.57 (0.24)	2.32 (0.24)	0.25 (−0.09, 0.59)	2.91 (0.27)	2.77 (0.27)	0.13 (−0.20, 0.47)
Change from baseline in SGRQ total score	–	–	–	32.07 (1.032)	32.81 (1.021)	−0.74 (−2.35, 0.86)	31.74 (1.136)	32.43 (1.130)	−0.69 (−2.38, 1.00)
Change from baseline in mean daily number of puffs	–	–	–	–	–	–	−1.51 (0.129)	−1.48 (0.127)	−0.03 (−0.26, 0.21)
Percentage of days with no rescue medication	–	–	–	–	–	–	60.32 (2.458)	59.36 (2.418)	0.96 (−3.52, 5.45)
CAT total score	–	–	–	11.7 (0.43)	11.5 (0.42)	0.3 (−0.4, 0.9)	11.1 (0.46)	11.2 (0.46)	−0.2 (−0.9, 0.6)

Notes: Data are presented as the LSM (SE); treatment differences are presented as the LSM (95% CI).

*** P<0.001.

Abbreviations: od, once daily; SFC, salmeterol/fluticasone; bid, twice daily; FEV₁, forced expiratory volume in 1 second; AUC, area under the curve; FVC, forced vital capacity; TDI, transition dyspnea index; SGRQ, St George’s Respiratory Questionnaire; CAT, COPD assessment test; LSM, least square means; SE, standard error; CI, confidence interval.

Figure 3 Trough FEV₁ on day 1 and at weeks 12 and 26 (full analysis set).

Notes: Data are least square means ± standard error; *P<0.001.

Abbreviations: bid, twice daily; FEV₁, forced expiratory volume in 1 second; od, once daily; SFC, salmeterol/fluticasone.

Figure 4 Forest plot of the treatment difference of trough FEV₁ (L) at week 26 by smoking history, baseline ICS use, COPD severity, and age for QVA149 and SFC after 26 weeks of treatment (LOCF).

Abbreviations: SFC, salmeterol/fluticasone; LSM, least square means; CI, confidence interval; N1, number of patients analyzed in the QVA149 group; N2, number of patients analyzed in the salmeterol/fluticasone group; ICS, inhaled corticosteroid; FEV₁, forced expiratory volume in 1 second; LOCF, last observation carried forward.

Table 3 Summary and analysis of COPD exacerbations over 26 weeks by treatment group (full analysis set)

Parameters	Moderate or severe COPD exacerbations
	QVA149 110/50 µg od (n=372)	SFC 50/500 µg bid (n=369)
Exacerbations per patient, n (%)
0	328 (88.2)	301 (81.6)
1	35 (9.4)	55 (14.9)
2	9 (2.4)	13 (3.5)
3	0	0
≥4	0	0
Total number of exacerbations	53	81
Total number of treatment years	179.2	174.9
Rate of exacerbations per year	0.30	0.46
Treatment comparison versus SFC
Ratio of rate (95% CI)	0.69 (0.48, 1.00)*

Note:

* P<0.05.

Abbreviations: SFC, salmeterol/fluticasone; CI, confidence interval, od, once daily; bid, twice daily.

Figure 5 Kaplan–Meier plots of the time to first moderate or severe COPD exacerbation over 26 weeks of treatment (full analysis set).

Abbreviations: SFC, salmeterol/fluticasone; HR, hazard ratio; CI, confidence interval; od, once daily; bid, twice daily.

Table 4 Annualized rate of moderate or severe COPD exacerbation by baseline COPD exacerbation history

Treatment	Annualized rate (95% CI)	Comparison	Rate ratio	95% CI	P-value
With COPD exacerbation history at baseline
QVA149 110/50 μg od (n=61)	0.49 (0.29, 0.82)	QVA149/SFC	0.60	(0.33, 1.08)	0.086
SFC 50/500 μg bid (n=93)	0.81 (0.56, 1.19)
Without COPD exacerbation history at baseline
QVA149 110/50 μg od (n=311)	0.23 (0.16, 0.33)	QVA149/SFC	0.76	(0.46, 1.24)	0.266
SFC 50/500 μg bid (n=276)	0.30 (0.21, 0.43)

Notes: Rate ratio, its 95% CI, and P-value are from a negative binomial regression model: Log (exacerbation rate) = treatment + baseline ICS use (yes/no) + baseline total symptom score + FEV₁ reversibility components. Log (length of time in the study) is included in the model as an offset term.

Abbreviations: CI, confidence interval; SFC, salmeterol/fluticasone; ICS, inhaled corticosteroid; od, once daily; bid, twice daily.

Table 5 Number (%) of AEs, SAEs, and deaths (safety set)

Parameters	QVA149 110/50 µg od N=372	SFC 50/500 µg bid N=369
Any AE	149 (40.1)	175 (47.4)
Any AEs in ≥1.5% of any group
COPD worseninga	75 (20.2)	97 (26.3)
Nasopharyngitis	30 (8.1)	45 (12.2)
Upper respiratory tract infection	13 (3.5)	26 (7.0)
Bronchitis	7 (1.9)	4 (1.1)
Pneumonia	3 (0.8)	10 (2.7)
Dyspnea	2 (0.5)	6 (1.6)
Oropharyngeal pain	2 (0.5)	6 (1.6)
AEs leading to discontinuation	12 (3.2)	17 (4.6)
COPD worsening	3 (0.8)	7 (1.9)
Any SAE	20 (5.4)	35 (9.5)
COPD	6 (1.6)	17 (4.6)
SAEs leading to discontinuation	9 (2.4)	11 (3.0)
Non-SAE(s) leading to discontinuation	3 (0.8)	7 (1.9)
Deaths	2 (0.5)	0

Notes:

a Including COPD exacerbations. Data are shown as n (%).

Abbreviations: AE, adverse event; SAE, serious adverse event; SFC, salmeterol/fluticasone; od, once daily; bid, twice daily.