Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naïve Extensive-Stage Small Cell Lung Cancer : A Phase 2 Randomized Study
©2021 American Association for Cancer Research..
PURPOSE: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naïve, 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 27(2021), 14 vom: 15. Juli, Seite 3884-3895 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Byers, Lauren Averett [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.03.2022 Date Revised 31.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1158/1078-0432.CCR-20-4259 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM325006474 |
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| 100 | 1 | |a Byers, Lauren Averett |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naïve Extensive-Stage Small Cell Lung Cancer |b A Phase 2 Randomized Study |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 31.03.2022 | ||
| 500 | |a Date Revised 31.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2021 American Association for Cancer Research. | ||
| 520 | |a PURPOSE: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naïve, extensive-stage small cell lung cancer (ED-SCLC) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Gans, Steven |e verfasserin |4 aut | |
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| 700 | 1 | |a Fujimoto, Junya |e verfasserin |4 aut | |
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| 700 | 1 | |a Dunbar, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Kingston |e verfasserin |4 aut | |
| 700 | 1 | |a He, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Sehgal, Vasudha |e verfasserin |4 aut | |
| 700 | 1 | |a Glasgow, Jaimee |e verfasserin |4 aut | |
| 700 | 1 | |a Bach, Bruce Allen |e verfasserin |4 aut | |
| 700 | 1 | |a Ellis, Peter M |e verfasserin |4 aut | |
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