Randomized trial of cisplatin and etoposide in combination with veliparib or placebo for extensive stage small cell lung cancer: ECOG-ACRIN 2511 study.

Abstract

8505 Background: Veliparib, a potent inhibitor of Poly (ADP) ribose polymerase (PARP) enzyme potentiates standard chemotherapy against small cell lung cancer (SCLC) in preclinical studies. We evaluated the combination of veliparib (V) with cisplatin/etoposide (CE) doublet for first-line therapy of extensive stage SCLC (ES-SCLC). Methods: Patients with ES-SCLC stratified by gender and serum LDH levels, were randomized to receive four 3-wk cycles of CE (75mg/m2 and 100 mg/m2) along with V (100mg bid on d1-7) or placebo (P). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS). Using an overall one-sided 0.10 level logrank test, this study had 88% power to detect a 37.5% reduction in the PFS hazard rate. Results: 128 eligible pts were enrolled across 33 US sites. Median age, 66 yrs; men, 52%; PS 0/1 (29%/71%). The estimated median PFS was 6.1 m vs. 5.5 m [unstratified HR: 0.75; 1-sided p = 0.06) favoring CE+V. The median OS was 10.3 m vs. 8.9 m respectively for CE+V and CE+P [stratified HR: 0.83 (80% CI 0.64-1.07); 1-sided p = 0.17]. There was a significant treatment by strata interaction in PFS: male pts with high LDH derived benefit [PFS HR of 0.34 (80% CI: 0.22-0.51)]; among pts not in this strata: PFS HR = 0.81 (80% CI: 0.60-1.09). The best objective response rate was 71.9% vs. 65.6% (2-sided p = 0.57). Salient grade ≥3 adverse events occurring in 5% of patients are summarized in the table below. Analysis of tumor samples for predictive biomarkers is planned. Conclusions: The addition of veliparib to doublet chemotherapy was associated with improved PFS in patients with extensive stage SCLC. Clinical trial information: NCT01642251. [Table: see text]