Pietanza MC, et al. - In this phase 2, randomized, double-blind study, researchers investigated the benefit on 4-month progression-free survival (PFS) of treatment with veliparib ( a poly [ADP-ribose] polymerase [PARP] inhibitor) added to temozolomide (TMZ) in patients with recurrent small-cell lung cancer (SCLC). They found that both treatment arms (TMZ/veliparib and TMZ/placebo) did not differ in terms of 4-month PFS and median overall survival (OS), whereas a significant improvement in overall response rate (ORR) was observed with TMZ/veliparib. In those treated with TMZ/veliparib, an association of SLFN11 expression with improved PFS and OS was observed, inferring a promising biomarker of PARP-inhibitor sensitivity in SCLC.

Methods

• This study included 104 patients with recurrent SCLC randomized 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m²/day, days 1 to 5, of a 28-day cycle until unacceptable toxicity, disease progression, or withdrawal of consent.
• Using imaging at weeks 4 and 8, and every 8 weeks thereafter, researchers determined the response.
• The primary end point was improvement in PFS at 4 months, and secondary objectives included overall response rate (ORR), overall survival (OS), and safety and tolerability of veliparib with TMZ.
• PARP-1 and SLFN11 immunohistochemical expression, MGMT promoter methylation, and circulating tumor cell quantification were included as exploratory objectives.

Results

• Findings revealed that 4-month PFS did not significantly differ between TMZ/veliparib (36%) and TMZ/placebo (27%; P=.19), and no significant improvement was seen in median OS with TMZ/veliparib (8.2 months; 95% CI, 6.4 to 12.2 months; v 7.0 months; 95% CI, 5.3 to 9.5 months; P=.50).
• However, they found significantly higher ORR in patients receiving TMZ/veliparib vs TMZ/placebo (39% v 14%; P=.016).
• With TMZ/veliparib vs TMZ/placebo, grade 3/4 thrombocytopenia and neutropenia was more common: 50% vs 9% and 31% vs 7%, respectively.
• Patients with SLFN11-positive tumors treated with TMZ/veliparib showed significantly prolonged PFS (5.7 v 3.6 months; P=.009) and OS (12.2 v 7.5 months; P=.014).