Neoadjuvant Therapy in Triple-Negative Breast Cancer
In a phase III trial (BrighTNess) reported in The Lancet Oncology, Loibl et al found that the addition of the PARP inhibitor veliparib to carboplatin and paclitaxel in neoadjuvant therapy did not increase pathologic complete response rate in women with triple-negative breast cancer.
Study Details
In the double-blind trial, 634 patients with previously untreated stage II or III triple-negative breast cancer who were candidates for potentially curative surgery from 145 sites in 15 countries were randomized 2:1:1 between April 2014 and March 2016 to receive one of three segment 1 neoadjuvant regimens: paclitaxel (80 mg/m² weekly for 12 doses) plus carboplatin (AUC = 6 every 3 weeks for four cycles) plus the PARP inhibitor veliparib (50 mg orally twice a day; n = 316); paclitaxel plus carboplatin plus veliparib-placebo (n = 160); or paclitaxel plus carboplatin-placebo plus veliparib-placebo (n = 158). All patients then received doxorubicin and cyclophosphamide every 2 to 3 weeks for four cycles in segment 2. Randomization for segment 1 was stratified by germline BRCA mutation status, nodal stage, and planned schedule of doxorubicin and cyclophosphamide administration.
The primary endpoint was pathologic complete response in breast and lymph nodes assessed by site pathologists on intention-to-treat analysis. The results are the first reported for the ongoing trial, with a data cutoff in December 2016.
Pathologic Complete Response
Proportions of patients achieving pathologic complete response were 53% in the paclitaxel, carboplatin, and veliparib group vs 31% in the paclitaxel alone group (P < .0001) and vs 58% in the carboplatin plus paclitaxel group (P = .36).
Toxicity
Grade 3 or 4 adverse events and serious adverse events were more common in patients receiving carboplatin, with veliparib not appearing to markedly increase toxicity. Overall, the most common grade 3 or 4 events were neutropenia (56%), anemia (29%), and thrombocytopenia (12%) during complete neoadjuvant therapy, and febrile neutropenia (15%) during doxorubicin-cyclophosphamide treatment. Overall, the most common serious adverse events were febrile neutropenia (13%) and anemia (3%).
The investigators concluded, “The addition of veliparib plus carboplatin to neoadjuvant weekly paclitaxel followed by doxorubicin and cyclophosphamide…showed a substantial, clinically significant improvement of [pathologic] complete response in the breast and resected lymph nodes compared with paclitaxel alone followed by doxorubicin and cyclophosphamide…However, the addition of veliparib to neoadjuvant carboplatin plus paclitaxel…did not improve the proportion of patients with [pathologic] complete response…compared with paclitaxel plus carboplatin…, suggesting that the improvement in observed [pathologic] complete response was due to carboplatin, without a substantial contribution from veliparib at the 50 mg dose and twice daily schedule…”
They further stated, “Increased toxicities with the addition of carboplatin (with or without veliparib) to paclitaxel were manageable and did not substantially affect treatment delivery of paclitaxel followed by doxorubicin and cyclophosphamide. Given the consistent results with previous studies, the addition of carboplatin appears to have a favourable risk to benefit profile and might be considered as a potential component of neoadjuvant chemotherapy for patients with high-risk, triple-negative breast cancer.”
The study was funded by AbbVie.
Sibylle Loibl, MD, of the German Breast Group, Neu-Isenburg, is the corresponding author for The Lancet Oncology article.
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