MD Conference Express - ELCC 2015 - (Page 11)
Veliparib Plus Platinum Therapy
Promising in NSCLC Phase 2 Trial
Table 1. Dose Regimen and Cycles
Dose regimen
Veliparib 120 mg or placebo BID on days 1 to 7 of 21
Carboplatin: 6 mg/mL/min on day 3 of 21
Paclitaxel: 200 mg/m2 on day 3 of 21
Cycle
Up to six 21-day cycles
Mean no. of
cycles
CP: 4.5 for carboplatin + 4.5 for paclitaxel
VCP: 4.5 for carboplatin + 4.3 for paclitaxel
Written by Francesca Coltrera
A phase 2 randomized trial [NCT01560104] suggests that
combining carboplatin and paclitaxel with veliparib-an
oral poly (ADP-ribose) polymerase (PARP) inhibitor-may
modestly extend progression-free survival (PFS) in certain patients with advanced non-small cell lung cancer
(NSCLC), and a phase 3 trial has been initiated. Giorgio
V. Scagliotti, MD, PhD, University of Turin, Turin,
Italy, discussed the results of a study based on a poster
by Julien Mazières, MD, PhD, Larrey Hospital-CHU,
Toulouse, France, and colleagues.
PARP enzymes are essential to DNA repair pathways. PARP inhibitors act to undermine repairs to
chemotherapy-induced DNA damage. In preclinical
models, veliparib boosted efficacy of DNA-damaging
platinum therapies. Some previous clinical trials-such
as ECLIPSE [Spigel D et al. J Thorac Oncol. 2013], which
combined iniparib with gemcitabine and carboplatin-
indicated that PARP inhibitors may have only a marginal
role to play in treating lung cancer, Prof Scagliotti commented. However, he added, BRCA-like behavior seen in
certain tumors suggests potentially wider applications
for PARP inhibitors.
Patients eligible for this multicenter double-blind trial
had squamous or nonsquamous NSCLC, ≥ 1 measurable
NSCLC lesion on computed tomography scan, no history of metastasis to the brain or primary central nervous
system tumors on baseline magnetic resonance imaging,
and an ECOG performance status ≤ 1. The investigators
stratified patients by histology (49% squamous NSCLC)
and smoking history (60% reported smoking within a
year of beginning the study). Sixty-four percent of participants were men.
Among the study exclusions were 2 confirmed EGFR
mutations (either exon 19 deletion or L858R mutation in
exon 21), although patients with wild-type EGFR, status
unknown, or other EGFR mutations were deemed eligible.
The primary end point was the effect of veliparib vs
placebo on PFS. Secondary end points were overall survival (OS), objective response rate, duration of overall
response, and regimen safety and tolerability.
In a 2:1 ratio, 158 patients were randomly assigned
to receive carboplatin + paclitaxel (CP; n = 53) or veliparib + carboplatin + paclitaxel (VCP; n = 105; Table 1).
Full chest and abdomen computed tomography scans
were performed every 6 weeks and at the last visit to
assess response based on the RECIST version 1.1 criteria
[Eisenhauer EA et al. Eur J Cancer. 2009].
CP, carboplatin + paclitaxel; VCP, veliparib + carboplatin + paclitaxel.
Table 2. Trend in Squamous Subgroup Favors Veliparib
End Point
CP
VCP
HR (95% CI)
Progression-free survival
4.2
5.8
0.71 (0.50 to 1.13)
Nonsquamous
5.0
4.3
0.94 (0.52 to 1.71)
Squamous
4.1
6.1
0.50 (0.24 to 1.04)
CP, carboplatin + paclitaxel; VCP, veliparib + carboplatin + paclitaxel.
Adverse events (AEs) were common in the CP and
VCP groups (any grade AE: 89% and 96%, respectively;
≥ grade 3 AE: 58% and 67%, respectively). Discontinuation due to AEs was 17% (CP) and 13% (VCP).
When data were analyzed, there was a statistically
nonsignificant trend toward improvement in the primary end point, PFS, in favor of the veliparib-containing
arm, with most of that improvement apparently coming in patients with squamous cell carcinoma (Table 2).
There was also a trend toward improvement in OS favoring veliparib, although this also failed to reach statistical significance (9.1 months with CP vs 11.7 months with
VCP; HR, 0.80; 95% CI, 0.54 to 1.18). Furthermore, duration of response was 3.3 and 6.9 months in the CP and
VCP groups, respectively (HR, 0.11; 95% CI, 0.03 to 0.50).
Combining veliparib with carboplatin and paclitaxel
was well tolerated and offered modest though statistically insignificant improvements in PFS and OS in
patients with squamous NSCLC. Given this encouraging
trend, a phase 3 trial for this subgroup has begun.
TIME Trial: Efficacy of TG4010
Immunotherapy With First-Line
Chemotherapy in NSCLC
Written by Anita Misra-Press, PhD
Lung cancer is emerging as a promising target for
immunotherapy, with the PD-1 inhibitor nivolumab
just recently approved by the FDA. Two categories
of novel immunotherapies being evaluated include
Peer-Reviewed Highlights From the European Society for Medical Oncology 2015 European Lung Cancer Conference
11
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