This article is more than 5 years old. Information may no longer be current.
Addition of veliparib to chemotherapy shows modest efficacy in small cell lung cancer
Click Here to Manage Email Alerts
The addition of veliparib to frontline chemotherapy improved PFS among patients with extensive-stage small cell lung cancer, according to results of a randomized, phase 2 trial published in Journal of Clinical Oncology.
However, the modest PFS improvement observed with veliparib (ABT-888, AbbVie), a poly(ADP-ribose) polymerase inhibitor, compared with placebo did not translate to a reduction in overall mortality, researchers noted.
“Systemic chemotherapy with a platinum and etoposide combination remains the most commonly used frontline treatment of extensive-stage small cell lung cancer,” Taofeek Owonikoko, MD, PhD, MSCR, professor of hematology and medical oncology at Emory University School of Medicine, and colleagues wrote. “Although this regimen induces objective tumor response in 50% to 70% of patients, the response is not durable.”
Owonikoko and colleagues analyzed 128 patients (median age, 66 years; 52% men) with extensive-stage small cell lung cancer who were stratified by sex and serum lactate dehydrogenase levels. Researchers randomly assigned patients to two groups: one that received four 3-week cycles of cisplatin (75 mg/m2 IV on day 1), etoposide (100 mg/m2 on days 1-3) and veliparib (100 mg orally twice per day on days 1-7) and another group that received the same chemotherapy regimen in combination with placebo.
The primary endpoint was PFS.
Results showed median PFS for the veliparib group was 6.1 months (95% CI, 5.9-6.7) compared with 5.5 months (95% CI, 5-6.1) for the placebo group. The unstratified HR was 0.75 (80% CI, 0.59-0.95), which was not statistically significant, but the observed stratified HR for PFS of 0.63 (one-sided P = .01) favored the veliparib group.
Men with high lactate dehydrogenase levels achieved a significant PFS benefit (HR = 0.34; 80% CI, 0.22-0.51); however, there was no evidence of any benefit among patients in other strata.
“We hypothesize that this cohort probably contained a sufficient proportion of patients with small cell lung cancer who harbored some biologic vulnerability to this therapeutic strategy,” researchers wrote.
By the time of analysis, 51 patients in the veliparib group and 54 patients in the placebo group had died.
Median follow-up among the surviving patients was 18.5 months.
Median OS was 10.3 months (95% CI, 8.9-12) in the veliparib group and 8.9 months (95% CI, 8.3-11.3) in the placebo group. There was no significant difference in OS by strata.
The overall response rate was 71.9% in the veliparib group and 65.6% in the placebo group.
Adverse events were consistent among both groups with two exceptions: the veliparib group experienced higher rates of grade 3 CD4 lymphopenia (8% vs. 0%) and grade 3 or 4 neutropenia (49% vs. 32%).
“Although the initial result of our study is promising, additional confirmation in a larger definitive study is warranted, given the mixed results reported by other studies of PARP inhibitors in this patient population,” Owonikoko and colleagues wrote. – by John DeRosier
Disclosures: NCI funded this study. Owonikoko reports consultant/advisory roles with AbbVie, Bristol-Myers Squibb, Celgene, Eisai, Eli Lilly, G1 Therapeutics, MedImmune, Novartis, Sandoz, Seattle Genetics and Takeda. Please see the study for all other authors’ relevant financial disclosures.
Read more about
Click Here to Manage Email Alerts