Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non–Small Cell Lung Cancer

DOI: 10.1158/1078-0432.CCR-15-3069 Published April 2017

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Figure 1.
CONSORT diagram. ^aOne declining performance status; 1 death. Carbo, carboplatin.
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Figure 2.
Best percentage change in the sum of target lesions sizes. A, Veliparib BID and carbo/paclitaxel (ORR, 32.4%; 95% CI, 23.6–42.2). B, Placebo BID and carbo/paclitaxel (ORR, 32.1%; 95% CI, 19.9–46.3). Carbo, carboplatin.

Table 1.

Demographics and baseline characteristics

Characteristic	Placebo BID and carbo/paclitaxel (N = 53)	Veliparib BID and carbo/paclitaxel (N = 105)
Median age (range), y	62 (46–79)	63 (33–84)
Sex, n (%)
Male	32 (60)	75 (71)
Female	21 (40)	30 (29)
Race
White	52 (98)	102 (97)
Black	1 (2)	2 (2)
American Indian/Alaskan Native	0 (0)	1 (1)
Histology, n (%)
Squamous	25 (47)	51 (49)
Nonsquamous	28 (53)	54 (51)
Smoking history, n (%)
Current	31 (58)	64 (61)
Former	14 (26)	28 (27)
Never	8 (15)	13 (12)
EGFR status, n (%)
Wild-type	49 (92)	91 (87)
Missing	4 (8)	14 (13)
Tumor burden at time of enrollment, n (%)
Locally advanced	15 (28)	22 (21)
Metastatic	38 (72)	83 (79)
Baseline ECOG, n (%)
0	17 (32)	35 (33)
1	36 (68)	70 (67)

Table 2.

Summary of AEs

AEs	Placebo BID and carbo/paclitaxel (N = 52)	Veliparib BID and carbo/paclitaxel (N = 105)
Any grade AE, n (%)	46 (89)	101 (96)
Any grade ≥3 AE, n (%)	30 (58)	72 (69)
Any SAE	12 (23)	28 (27)
Alopecia	22 (42)	41 (39)
Neutropenia	15 (29)	38 (36)
Anemia	21 (40)	33 (31)
Nausea	13 (25)	29 (28)
Peripheral neuropathy	13 (25)	25 (24)
Fatigue	13 (25)	24 (23)
Arthralgia	7 (13)	20 (19)
Dyspnea	6 (12)	16 (15)
Decreased appetite	9 (17)	14 (13)
Diarrhea	8 (15)	13 (12)
Thrombocytopenia	8 (15)	13 (12)
Myalgia	4 (8)	13 (12)
Pain	6 (12)	12 (11)
Constipation	7 (13)	9 (9)
Cough	8 (15)	8 (8)
Unbalanced AE, n (%)
Leukopenia	0 (0)	12 (11)
Grade ≥3 AEs, n (%)
Neutropenia	12 (23)	20 (19)
Anemia	5 (10)	11 (10)
Alopecia	3 (6)	7 (7)
Leukopenia	0 (0)	6 (6)
Thrombocytopenia	3 (6)	5 (5)
Nausea	0 (0)	4 (4)
Hyperkalemia	1 (2)	4 (4)
Arthralgia	0 (0)	3 (3)
Fatigue	0 (0)	3 (3)
Hypersensitivity	0 (0)	3 (3)
Hyponatremia	1 (2)	2 (2)
Myalgia	0 (0)	2 (2)
Weight loss	0 (0)	2 (2)

NOTE: Analyses of safety were performed using data from the 157 patients who received at least 1 dose of study drug. Toxicity of any grade occurring in ≥10% of patients and grade ≥3 occurring in >1 patient are reported.
Abbreviations: carbo, carboplatin; SAE, serious adverse event.

Table 3.

Reasons for discontinuation of study drug

Primary reason for veliparib/placebo discontinuation	Placebo BID and carbo/paclitaxel (N = 53)	Veliparib BID and carbo/paclitaxel (N = 105)
Completed treatment	27 (50.9%)	51 (48.6%)
Progression of disease	13 (24.5%)	22 (21.0%)
Adverse event related to progression	2 (3.8%)	8 (7.6%)
Adverse event not related to progression	10 (18.9%)	14 (13.3%)
Withdrew consent	2 (3.8%)	9 (8.6%)
Lost to follow-up	0	1 (1.0%)
Other	1 (1.9%)	6 (5.7%)

Table 4.

Overview of results for primary and secondary endpoints

	PFS median (95% CI), mo	OS median (95% CI), mo	ORR, % (95% CI)	DOR median (95% CI), mo
Placebo BID and carbo/paclitaxel (N = 53)	4.2 (3.1–5.6)	9.1 (5.4–12.3)	32.1 (19.9–46.3)	4.3 (2.8–NA)
Squamous (n = 25)	4.1 (2.8–NA)	8.4 (5.0–12.9)
Nonsquamous (n = 28)	5.0 (2.8–5.7)	11.1 (4.8–14.6)
Veliparib BID and carbo/paclitaxel (N = 105)	5.8 (4.3–6.5)	11.7 (8.8–13.7)	32.4 (23.6–42.2)	6.9 (4.5–7.0)
Squamous (n = 51)	6.5 (4.4–8.4)	10.3 (8.3–13.2)
Nonsquamous (n = 54)	5.6 (2.8–6.4)	12.8 (8.0–17.2)
HR (95%CI)
All patients (N = 158)	0.72 (0.45–1.15)	0.80 (0.54–1.18)		0.47 (0.16–1.42)
Squamous (n = 76)	0.54 (0.26–1.12)	0.73 (0.43–1.24)
Nonsquamous (n = 82)	0.87 (0.48–1.59)	0.90 (0.51–1.58)
Adjusted HR^a (95% CI)
All patients (N = 158)	0.56 (0.35–0.90)	0.72 (0.49–1.07)
Squamous (n = 76)	0.43 (0.20–0.94)	0.70 (0.39–1.21)
Nonsquamous (n = 82)	0.73 (0.39–1.36)	0.77 (0.43–1.37)

Table 5.

Post-study therapies

Post-study therapy	Placebo BID and carbo/paclitaxel (N = 53)	Veliparib BID and carbo/paclitaxel (N = 105)
Without any therapy	31 (58.5%)	46 (43.8%)
With at least one therapy	22 (41.5%)	59 (56.2%)
Type of medications in post-study therapy^a
Docetaxel	5 (9.4%)	14 (13.3%)
Erlotinib	2 (3.8%)	14 (13.3%)
Gemcitabine	4 (7.5%)	14 (13.3%)
Pemetrexed	5 (9.4%)	21 (20.0%)
Other	12 (22.6%)	40 (38.1%)

Abbreviation: carbo, carboplatin.
↵^aPatients who were on multiple medications in a therapy are counted under each medication.

Supplementary Data

Supplemental Materials - Supplemental Table 1. Demographics and baseline characteristics by histology: squamous cell Supplemental Table 2. Demographics and baseline characteristics by histology: non-squamous cell Supplemental Table 3. Mean {plus minus} SD pharmacokinetic parameters of veliparib on cycle 1 day 3 Supplemental Table 4. Mean {plus minus} SD (median) plasma concentrations of paclitaxel and carboplatin at 5 min before ending paclitaxel and carboplatin infusions, respectively Supplemental Figure 1: Progression-free survival (A) and overall survival (B) in responders and non-responders