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Combination demonstrates activity in extensive stage small cell lung cancer
CHICAGO — The combination of veliparib and cisplatin/etoposide conferred benefit to patients with extensive stage small cell lung cancer, according to results from the phase 2 ECOG-ACRIN 2511 study.
“In preclinical studies, the inhibition of PARP enzyme activity through genetic ablation of pharmacologic agents sensitized cancer cells to DNA damaging chemotherapy as well as ionized radiation,” Taofeek K. Owonikoko, MD, PhD, an associate professor of hematology and medical oncology at Emory University School of Medicine, said during a presentation at the ASCO Annual Meeting. “We are all very aware of the poor outcomes for small cell lung cancer patients – principally due to limited therapeutic options in this disease.”
Owonikoko and colleagues conducted a randomized study of 128 patients (median age, 66 years; men, 52%) with newly diagnosed extensive stage small cell lung cancer to evaluate if the addition of veliparib (ABT-888, AbbVie) — an investigational, oral PARP inhibitor — to standard chemotherapy would lead to improved outcomes.
All study participants were stratified by gender and serum lactate dehydrogenase levels.
Patients were randomized to receive four 3-week cycles of cisplatin 75 mg/m2 and etoposide 100 mg/m2 in combination with veliparib 100 mg on days 1 through 7, or placebo.
Progression-free survival served as the primary endpoint. Secondary endpoints included overall response rate, OS and safety.
Researchers reported an estimated median PFS of 6.1 months for patients who received veliparib versus 5.5 months in patients who received placebo. Additionally, investigators reported a median OS of 10.3 months in patients who received the veliparib combination therapy compared with a median OS of 8.9 months in patients who received placebo (stratified HR = 0.83; 80% CI, 0.64-1.07).
Males with high serum lactate dehydrogenase levels derived the greatest PFS benefit from veliparib combination treatment (HR = 0.34; 80% CI, 0.22-0.51), according to Owonikoko.
The most common grade 3 adverse events reported by patients who received veliparib included neutropenia (20%) and anemia (17%); and the most common grade 4 events included neutropenia (29% and leukopenia (11%).
Patients who received placebo most commonly reported experiencing grade 3 neutropenia (14%), anemia (12%) and leukopenia (12%). Neutropenia (18%) was the most common grade 4 adverse event patients in this group reported.
“ECOG 2511 signals potential benefits of the addition of veliparib – a PARP inhibitor – to chemotherapy compared to treating patients with chemotherapy alone,” Owonikoko said. “Given the strata by treatment interaction, we anticipate that biomarker enrichment to prospectively identify the subgroup of patients most likely to benefit from this strategy would inform the best way to realize this potential benefit going forward.” – by Ryan McDonald
Reference:
Owonikoko TK, et al. Abstract 8505. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: Owonikoko reports serving as a consultant or advisor for Abbvie, Celgene, Eisai, G1 Therapeutics, Genentech/Roche, Lilly, Novartis, Sandoz and Takeda. Additionally, Owonikoko reports receiving research funding through his institution from Abbvie, Astellas Pharma, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, Celgene, G1 Therapeutics, Novartis, Regeneron and Stemcentrix.