Winship Cancer Institute of Emory University, Atlanta, GA
Suresh S. Ramalingam , Normand Blais , Julien Mazières , Martin Reck , C. Michael Jones , Erzsebet Juhasz , Laszlo Urban , Sergey Orlov , Fabrice Barlesi , Ebenezer A. Kio , Ulrich Keilholz , Jane Qian , Qin Qin , Martin Dunbar , Hao Xiong , Rajendar K. Mittapalli , Peter Ansell , Mark D. McKee , Vincent L. Giranda , Vera Gorbunova
Background: Tobacco-related non-small cell lung cancer (NSCLC) is associated with reduced survival and greater genomic instability. Veliparib (V) is a PARP inhibitor that augments platinum-induced DNA damage in preclinical studies, and a recent Ph 2 trial of advanced NSCLC trended to improved survival (HR 0.80; CI 0.54–1.18) when V was added to carboplatin (C) and paclitaxel (P). Here we report outcomes based on smoking status from a randomized Ph 2 study of CP with either V or placebo in advanced NSCLC. Methods: Patients (pts) with previously untreated advanced/metastatic NSCLC were randomized 2:1 to CP with either V at 120 mg BID or placebo (pre-specified stratification by histology and smoking history). Cotinine (COT) was measured in pt plasma samples as an index of recent tobacco use. Results: Of 158 pts, 68% were male, and 49% had squamous NSCLC. At study entry, 60% of pts were self-reported current smokers (CS), 27% former smokers, and 13% never smoked. There were no significant differences in V PK parameters between the COT-high and low pts.Most common AE in CS were neutropenia (41% VCP; 27% CP), alopecia (36%; 33%), and anemia (31%; 40%). G3/4 AEs were elevated in CS treated with VCP vs CP (66% vs. 40%, p=0.026); all-grade AEs and SAEs were similar between the two groups. In a COT sensitivity analysis of OS, HR VCP/CP for COT-high was 0.52 (0.29–0.92) and COT-low was 1.07 (0.63–1.81). Conclusions: Smoking status was a strong predictor of efficacy for veliparib-chemotherapy combination in advanced NSCLC. No differences in PK of V were seen based on plasma COT; toxicity of VCP was acceptable regardless of smoking history. A Ph 3 study has been initiated in pts with smoking history. Clinical trial information: NCT01560104
Median months (95% CI) | CP CS, n=31 Former, 14 Never, 8 | VCP CS, n=64 Former, 28 Never, 13 | HR VCP/CP | HRadj VCP/CP (Adjusted for gender and ECOG PS) | |
---|---|---|---|---|---|
PFS | CS Former Never | 3.3 (1.4–4.2) NA (3.3–NA) 5.6 (1.4–8.2) | 5.6 (4.1–7.0) 6.0 (2.4–NA) 6.4 (1.0–NA) | 0.38 (0.21–0.67) 2.10 (0.66–6.65) 1.03 (0.27–3.85) | 0.37 (0.21–0.68) 0.77 (0.20–3.06) 0.96 (0.21, 4.46) |
OS | CS Former Never | 5.4 (3.8–8.8) 14.6 (9.2–NA) NA (3.6–NA) | 12.5 (9.9–16.6) 8.6 (5.9–17.5) 13.2 (5.0–NA) | 0.43 (0.26–0.70) 1.62 (0.73–3.6) 1.34 (0.40–4.44) | 0.45 (0.27–0.76) 0.72 (0.27–1.92) 0.71 (0.18–2.74) |
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Abstract Disclosures
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