Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase 3 trial.
BACKGROUND: Primary analyses of the phase 3 BrighTNess trial showed addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC). Here,...
| Autores: | , , , , , , , , , , , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| Repositorio: | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| OAI Identifier: | oai:isabial.fundanetsuite.com:p8185 |
| Acesso em linha: | https://isabial.portalinvestigacion.com/publicaciones8185 https://www.sciencedirect.com/science/article/pii/S0923753422000187?via%3Dihub |
| Access Level: | acceso abierto |
| Palavra-chave: | (max 6): carboplatin neoadjuvant chemotherapy phase 3 triple-negative breast cancer veliparib |
| Resumo: | BACKGROUND: Primary analyses of the phase 3 BrighTNess trial showed addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC). Here, we report 4.5-year follow-up data from the trial. DESIGN: Women with untreated stage II-III TNBC were randomized (2:1:1) to paclitaxel (weekly for 12 doses) plus either: (a) carboplatin (every 3 weeks for four cycles) plus veliparib (twice daily); (b) carboplatin plus veliparib placebo; or (c) carboplatin placebo plus veliparib placebo. All patients then received doxorubicin and cyclophosphamide (AC) every 2?3 weeks for four cycles. The primary endpoint was pCR. Secondary endpoints included event-free survival (EFS), overall survival (OS), and safety. Since the co-primary endpoint of increased pCR with carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel was not met, secondary analyses are descriptive. RESULTS: Of 634 patients, 316 were randomized to carboplatin plus veliparib with paclitaxel, 160 to carboplatin with paclitaxel, and 158 to paclitaxel. With median follow-up of 4.5 years, the hazard ratio [HR] for EFS for carboplatin plus veliparib with paclitaxel versus paclitaxel was 0.63 (95% confidence interval [CI] 0.43?0.92, P=0.02), but 1.12 (95% CI 0.72?1.72, P=0.62) for carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel. In post hoc analysis, HR for EFS was 0.57 (95% CI 0.36?0.91, P=0.02) for carboplatin with paclitaxel versus paclitaxel. OS did not differ significantly between treatment arms, nor did rates of myelodysplastic syndromes, acute myeloid leukemia, or other secondary malignancies. CONCLUSION: Improvement in pCR with addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without increasing the risk of second malignancies, while adding veliparib did not impact EFS. These findings support the addition of carboplatin to weekly paclitaxel followed by AC neoadjuvant chemotherapy for early stage TNBC. |
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