The eagerly awaited results of the BrighTNess study confirm the benefit of adding carboplatin to standard chemotherapy in triple negative breast cancer (TNBC), but show no additional benefit with the PARP inhibitor velirapib.
In a phase 3 randomised controlled trial involving 634 women with TNBC, the proportion who achieved a pathological complete response was 58% for those receiving paclitaxel plus carboplatin, 53% for those receiving paclitaxel plus carboplatin and velirapib and 31% for those receiving paclitaxel alone.
Use of carboplatin was associated with more Grade 3 or 4 toxicities, but this did not substantially affect delivery of other chemotherapy. The addition of velirapib did not increase toxicity further.
The study authors, led by Dr Sibylle Loibl of the German Breast Group, said the findings confirmed the benefits of carboplatin seen in earlier Phase 2 studies such as the GeparSixto and CALGB trials, indicating it was “a reasonable option for patients with high-risk triple-negative breast cancer.”
“The BrighTNess findings provide important information that supports the inclusion of carboplatin as a component of a standard neoadjuvant regimen in patients with stage II–III triple-negative breast cancer for whom a major goal of treatment is achieving clinical and pathological response in the breast and regional nodes,” they said in Lancet Oncology.
The lack of incremental benefit seen with velirapib might be due to the dose of 50mg twice a day being too low, they suggested.
Other studies such as the BROCADE phase 2 trial had shown that a dose of 120mg velirapib could be tolerated, they noted.
“The collective experience with the addition of veliparib to paclitaxel plus carboplatin suggests that higher doses might be tolerable, which could be important in light of data suggesting that PARP trapping at sites of DNA damage is a crucial component of PARP inhibition,” they said.
It would also be important to confirm in follow up analyses the benefits of carboplatin on endpoints such as event free survival and overall survival in women with TNBC, they added.
“Additionally, the health-related quality of life analyses from BrighTNess, which will also be reported separately, will contribute important information to help to determine whether or not carboplatin should become a component of the global standard of care for patients with triple-negative breast cancer.”
In an accompanying commentary, Dr Giuseppe Curigliano, of the European institute of Oncology in Milan, said the BrighTNess trial findings raised the question of using carboplatin as targeted therapy in subgroups of patients with particular triple negative breast cancer subtypes.
“Once patients who are likely to benefit from the addition of platinum salts to neoadjuvant chemotherapy are better identified, the achievement of pathological complete responses might increase and, most importantly, fewer patients might have carboplatin-related toxicities,” he wrote.
The trial was funded by AbbVie, makers of velirapib.