Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naive Extensive-Stage Small Cell Lung Cancer: A Phase 2 Randomized Study

Lauren Averett Byers*, Dmitry Bentsion, Steven Gans, Konstantin Penkov, Choonhee Son, Anne Sibille, Harry Jm Groen, Taofeek K Owonikoko, Carl M Gay, Junya Fujimoto, Patricia de Groot, Martin Dunbar, Kingston Kang, Lei He, Vasudha Sehgal, Jaimee Glasgow, Bruce A Bach, Peter M Ellis

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

19 Citaten (Scopus)
86 Downloads (Pure)

Samenvatting

Purpose: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naive, extensive-stage small cell lung cancer (ED-SCLC).

Patients and Methods: Patients were randomized 1:1:1 to veliparib [240 mg twice daily (BID) for 14 days] plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control.

Results: Overall (N = 181), PFS was improved with veliparib throughout versus control [hazard ratio (HR), 0.67; 80% confidence interval (CI), 0.50-0.88; P = 0.059]; median PFS was 5.8 and 5.6 months, respectively. There was a trend toward improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR, 0.6; 80% CI, 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR, 1.43; 80% CI, 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, veliparib combination-only and control arms, most commonly hematologic.

Conclusions: Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting.

Originele taal-2English
Pagina's (van-tot)3884-3895
Aantal pagina's12
TijdschriftClinical Cancer Research
Volume27
Nummer van het tijdschrift14
Vroegere onlinedatum4-mei-2021
DOI's
StatusPublished - 15-jul.-2021

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