In the phase II ECOG-ACRIN 2511 trial reported in the Journal of Clinical Oncology, Owonikoko et al found that the addition of the poly (ADP ribose) polymerase (PARP) inhibitor veliparib to cisplatin/etoposide was associated with a modest but statistically significant improvement in progression-free survival in previously untreated patients with extensive-stage small cell lung cancer (SCLC).
In the double-blind trial, 128 eligible patients who received study treatment were randomly assigned between October 2013 and July 2015 to receive cisplatin/etoposide plus veliparib (n = 64) or placebo (n = 64). Treatment consisted of cisplatin 75 mg/m2 on day 1 and etoposide 100 mg/m2 on days 1 through 3 plus veliparib 100 mg twice daily or placebo on days 1 through 7 in 21-day treatment cycles. Randomization was stratified by sex and serum lactate dehydrogenase (LDH) levels.
The primary endpoint was progression-free survival.
Median follow-up of surviving patients at time of analysis was 18.5 months. Median progression-free survival was 6.1 months in the veliparib group vs 5.5 months in the control group (unstratified hazard ratio [HR] = 0.75, one-sided P = .06; stratified HR = 0.63, one-sided P = .01). Median overall survival was 10.3 vs 8.9 months (stratified HR = 0.83, one-sided P = .17). Overall response rates were 71.9% vs 65.6% (two-sided P = .57).
A significant treatment-by-strata interaction was observed for progression-free survival, with benefit in the veliparib group being significant among male patients with high LDH levels (HR = 0.34, 80% confidence interval [CI] = 0.22–0.51) but not significant in other strata (HR = 0.81, 80% CI = 0.60–1.09).
Treatment-related grade ≥ 3 adverse events that were more common in the veliparib group included neutropenia (49% vs 32%), anemia (19% vs 12%), leukopenia (19% vs 14%), hyponatremia (12% vs 7%), lymphopenia (8% vs 0%), and hyperglycemia (5% vs 0%). Grade ≥ 3 febrile neutropenia occurred in 5% vs 5% of patients.
The investigators concluded, “The addition of veliparib to frontline chemotherapy showed signal of efficacy in patients with [extensive-stage] SCLC and the study met its prespecified endpoint.”
They also noted, “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. There is an ongoing phase II study, M14-361, that uses a carboplatin-based chemotherapy doublet backbone in combination with veliparib. A larger definitive study to evaluate the value of this therapeutic strategy would be justified if the M14-361 study shows a similar signal of efficacy.”
Taofeek K. Owonikoko, MD, PhD, of Emory University, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute. The study authors’ full disclosures can be found at jco.ascopubs.org.
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