medwireNews: Some patients with extensive-stage small-cell lung cancer (SCLC) may benefit from the addition of the poly(ADP ribose) polymerase (PARP) inhibitor veliparib to standard chemotherapy, but further confirmation of its efficacy is needed, say researchers.
Taofeek Owonikoko (Emory University, Atlanta, Georgia, USA) and colleagues found that, during a median 18.5-month follow-up period, median progression free survival (PFS) was 6.1 months among 64 patients with extensive-stage SCLC who were randomly assigned to receive four 3-week cycles of intravenous cisplatin (75 mg/m2 on day 1) and etoposide (100 mg/m2 on days 1–3) plus oral veliparib (100 mg twice daily on days 1–7).
This compared with a PFS of 5.5 months among the 64 patients randomly assigned to receive cisplatin and etoposide in combination with placebo during the phase II ECOG-ACRIN 2511 Study.
When the data were analyzed on a non-stratified basis, the hazard ratio (HR) of 0.75 indicated no significant difference between the two treatment arms. However, when the data were stratified by sex and serum lactate dehydrogenase (LDH) levels, the HR was 0.63 in favor of the veliparib arm.
The researchers note that the difference between the unstratified and stratified HRs for PFS was unexpected and caused them to further examine the data. In this analysis, they found a significant treatment-by-strata interaction: only men with LDH levels above the upper limit of normal significantly benefited from the addition of veliparib, at a HR of 0.34.
Women with either normal or high LDH levels and men with normal LDH levels did not appear to benefit from additional treatment with the PARP inhibitor.
“There is no biologically rational explanation for the strong effect seen in the subset of male patients with elevated LDH levels,” Owonikoko and co-authors write in the Journal of Clinical Oncology.
“However, this subset is also the largest of the four strata, with approximately 60 patients. Therefore, we hypothesize that this cohort probably contained a sufficient proportion of patients with SCLC who harbored some biologic vulnerability to this therapeutic strategy,” they add.
Overall survival (10.3 vs 8.9 months) and the overall response rate (71.9 vs 65.6%) did not differ significantly between the veliparib and placebo arms.
The rates of grade 3 or higher adverse events were also similar between the two groups with the exception of grade 3 CD4 lymphopenia (8 vs 0%) and grade 3–4 neutropenia (49 vs 32%) which were more common with veliparib than with placebo.
“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 et al conclude.
By Laura Cowen
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