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Addition of Veliparib to Cisplatin/Etoposide in Extensive-Stage SCLC

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Key Points

  • The addition of veliparib to cisplatin/etoposide improved progression-free survival.
  • Median progression-free survival was 6.1 vs 5.5 months.

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).

Study Details

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.

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).

Adverse Events

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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