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Addition of Veliparib to Temozolomide in Recurrent Small Cell Lung Cancer

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Key Points

  • The addition of veliparib to temozolomide did not improve progression-free or overall survival among all patients,
  • Benefit was observed with the combination in patients with SLFN11-positive tumors.

In a phase II trial reported in the Journal of Clinical Oncology, Pietanza et al found no benefit of adding the PARP inhibitor veliparib to temozolomide (Temodar) in recurrent platinum-sensitive or platinum-refractory small cell lung cancer. Benefit was observed with the combination in the subgroup of patients with tumors positive for SLFN11 (a candidate predictive marker of sensitivity to DNA-damaging chemotherapy).

Study Details

In the double-blind trial, 104 patients from seven U.S. centers were randomized between August 2012 and February 2015 to receive oral temozolomide 150 to 200 mg/m2/d on days 1 to 5 plus oral veliparib 40 mg twice daily on days 1 to 7, or placebo in 28-day cycles until disease progression or unacceptable toxicity. Progression-free survival at 4 months was the primary endpoint. Approximately 60% of patients in both groups had refractory disease.

Progression-Free Survival and Response Rates

Progression-free survival at 4 months was 36% in the combination group vs 27% in the temozolomide group (P = .19). Median progression-free survival was 3.8 months vs 2.0 months (hazard ratio = 0.84, P = .39). Median overall survival was 8.2 months vs 7.0 months, P = .50). Among 23 patients with SLFN11-positive tumors, median progression-free survival (5.7 vs 3.6 months, P = .009) and overall survival (12.2 vs 7.5 months, P = .014) were prolonged with the combination. Overall response rates were 39% vs 14% (P = .016), including 41% vs 11% in platinum-sensitive patients and 37% vs 15% in platinum-refractory patients.

Toxicity

The combination group experienced more grade 3 or 4 thrombocytopenia (50% vs 9%) and neutropenia (31% vs 7%). Grade 3 or 4 nonhematologic toxicity was infrequent, with the most common being fatigue (4% vs 2%).

The investigators concluded, “Four-month [progression-free survival] and median [overall survival] did not differ between the two arms, whereas a significant improvement in [objective response rate] was observed with temozolomide/veliparib. SLFN11 expression was associated with improved [progression-free and overall survival] in patients receiving temozolomide/veliparib, suggesting a promising biomarker of PARP-inhibitor sensitivity in [small cell lung cancer].”

They noted that the higher response rates with the combination support additional studies of the regimen.

The study was supported by the Cancer Therapy Evaluation Program at the National Cancer Institute (NCI), NCI grants, philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shot Program, and others.

Lauren Averett Byers, MD, of the Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

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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