Iniparib benefits patients with metastatic triple-negative breast cancer
MedWire News: The addition of iniparib to gemcitabine and carboplatin chemotherapy provides significant clinical benefit to women with metastatic triple-negative breast cancer, US study data show.
Iniparib - an anticancer agent with poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) inhibitory activity - prolonged the duration of stable disease and time to death among women participating in the phase II clinical study, which compared the efficacy and safety of gemcitabine and carboplatin with or without iniparib.
Lead author Joyce O'Shaughnessy (Baylor Charles A Sammons Cancer Center, Dallas, Texas) and colleagues explain that PARP1 is an important regulator of the DNA base-excision-repair pathway.
"Preclinical studies have shown that combining PARP1 inhibitors with platinum chemotherapy agents, which induce DNA damage through adducts and cross-linking, potentiates chemotherapeutic cytotoxicity," they add.
In the present study, 123 patients with metastatic triple-negative breast cancer were randomly assigned to receive gemcitabine and carboplatin on days 1 and 8, with or without iniparib (5.6 mg/kg) on days 1, 4, 8, and 11. The regimen was repeated every 21 days.
The researchers assessed clinical benefit rate (CBR), defined as the objective response rate (complete or partial response) plus the stable disease rate for at least 6 months, as well as the safety of the two treatment regimens.
They found that patients treated with iniparib had a significantly higher CBR and overall response rate relative to those who did not receive iniparib, at 56% and 52% versus 34% and 32%, respectively.
In addition, the median progression-free and overall survival times were significantly longer in the iniparib group compared with the no-iniparib group, at 5.9 and 12.3 versus 3.6 and 7.7 months, respectively.
Of note, the rate of grade 3 or 4 adverse events did not differ significantly between the groups. The most frequent events included neutropenia, thrombocytopenia, anemia, and leukopenia.
"This phase II study provides proof of concept that the combination of iniparib with gemcitabine-carboplatin provides significant clinical benefit with a favorable safety profile in patients with metastatic triple-negative breast cancer," O'Shaughnessy and co-authors conclude in the New England Journal of Medicine.
"On the basis of these results, a phase III trial of iniparib plus chemotherapy in patients with metastatic triple-negative breast cancer, adequately powered to study overall survival and progression-free survival is being conducted," they add.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Laura Dean