AbbVie’s investigational oral PARP inhibitor veliparib was not effective against early-stage triple-negative breast cancer when given in combination with chemotherapy, the company recently announced.
Despite the drawback, AbbVie researchers believe there is a place for PARP inhibitors in cancers with abnormal DNA repair, including those with BRCA mutations.
The Phase 3 trial (NCT02032277) included 312 patients, randomized to receive various combinations of treatments or placebo. One group was treated with veliparib in combination with the two chemotherapies Paraplatin (carboplatin) and paclitaxel. Another group received placebo and the two chemotherapy treatments, and a third group received placebo and paclitaxel.
After this initial treatment, all patients received Adriamycin (doxorubicin) and cyclophosphamide.
The main outcome measure of the trial was a complete response. But even though AbbVie announced that the trial did not meet this endpoint, they did not disclose details. Instead, they referred to a future publication of results.
The same approach was tested in patients with lung cancer, but the treatment also failed in this group of patients.
“Research shows there is a role for PARP inhibitors in cancers associated with DNA repair deficits, such as those with BRCA mutations,” Gary Gordon, MD, PhD, and vice president of oncology clinical development at AbbVie, said in a press release.
“In these clinical trials, we wanted to explore whether a PARP inhibitor could augment chemotherapy in patients with squamous non-small cell lung cancer and triple negative breast cancer by disrupting the repair of cancer cells. Unfortunately, these data do not support the use of veliparib in combination with chemotherapy in these patients.”
The news is the second negative report of veliparib effectiveness in a short time. In December 2016, AbbVie announced that although the drug triggered a response in the majority of metastatic breast cancer patients, it did not lengthen progression-free survival.
However, the study was a Phase 2 trial (NCT01506609) and, at the time, researchers said the trial might have been too small to detect an effect. Instead, they put their hopes on an upcoming Phase 3 trial (NCT02163694).
The PARP (poly[ADP-ribose] polymerase) enzyme works to repair DNA damage in cells. The idea with veliparib was that by blocking the DNA repair system, the treatment will increase the likelihood that cancer cells die during chemotherapy.
It is not clear how the negative data will impact further development of the treatment.