BrighTNess: Long-Term Event-Free Survival Supports TNBC Neoadjuvant Carboplatin Use

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Event-free survival (EFS) results from the BrighTNess trial presented at the ESMO Congress 2021 confirm that the addition of carboplatin to neoadjuvant paclitaxel improves the outcomes of women with stage II/III triple-negative breast cancer (TNBC). 

Sibylle Loibl, from the German Breast Group in Neu-Isenburg, reminded delegates that the primary endpoint of pathological complete response (pCR) was previously reported in favour of combining paclitaxel and carboplatin with or without veliparib but that inclusion of the PARP inhibitor did not provide any additional benefit.  

The study’s design means that the current secondary analyses of long-term EFS, overall survival (OS), and postoperative second malignancies after a median follow-up of 4.5 years are therefore only “descriptive with nominal P-values”, she explained. 

The trial’s neoadjuvant regimens all included 12 weekly doses of paclitaxel 80 mg/m2 either given as a monotherapy, or in combination with four cycles of carboplatin AUC 6 mg/mL per minute every 3 weeks, or with carboplatin plus veliparib 50 mg twice daily. 

All participants then received four cycles of doxorubicin and cyclophosphamide, followed by surgery 2–8 weeks after their final chemotherapy dose. 

The 4-year EFS rate for the 316 patients who received the triplet regimen was 78.2% and this was significantly better than the 68.5% rate for the 158 patients given paclitaxel alone (hazard ratio [HR]=0.63) but comparable to the 79.3% rate for the 160 participants given paclitaxel plus carboplatin (nonsignificant HR=1.12). Post-hoc analysis indicated that paclitaxel plus carboplatin was significantly better than paclitaxel alone (HR=0.57). 

Further analysis indicated that trial participants from any treatment arm who achieved a pCR had a significantly better EFS than those who did not, at 11% versus 33% and a HR of 0.26. This association persisted when assessing patients with and without a germline BRCA mutation separately (HR=0.14 and 0.29, respectively). 

Overall, 12.0% of patients given paclitaxel, carboplatin and veliparib died during follow-up, as did a statistically comparable 10.0% of those given paclitaxel plus carboplatin and 13.9% of participants given only paclitaxel.  

Sibylle Loibl also reported that the three regimens had “manageable safety profiles” and were not associated with increased risk of myelodysplastic syndrome, acute myeloid leukaemia and other second primary malignancies. 

The presenter concluded that while the use of veliparib in the regimen did not impact pCR, EFS or OS, the “findings support the inclusion of carboplatin in neoadjuvant chemotherapy for stage II–III TNBC, irrespective of [germline]BRCA status.” 

Session discussant Monica Arnedos, from Institut Gustave Roussy in Villejuif, France, discussed the prior “lack of consensus” on the use of neoadjuvant platinum salts in TNBC and the impact of both the BrighTNess study findings and the likely approval for adjuvant PARP inhibition in patients with germline BRCA mutations. 

Citing the BROCADE 3 trial of metastatic breast cancer, she suggested that the addition of a PARP inhibitor to paclitaxel and carboplatin may show a benefit when given as a maintenance treatment after surgery. 

Monica Arnedos suggested that patients with moderate- or high-risk TNBC should receive neoadjuvant paclitaxel plus carboplatin, with the possibility of additional pembrolizumab based on results from the KEYNOTE-522 results. This should be followed by surgery and maintenance pembrolizumab, with use of olaparib in patients with germline BRCA mutations and capecitabine in those without a pCR, she recommended. 

For patients with low risk or who are unfit for this regimen research is required to “provide new de-escalation strategies”, the discussant concluded. 

Reference  

119O - Loibl S, Sikov W, Huober J, et al. Event-free survival, overall survival, and safety of adding veliparib plus carboplatin or carboplatin alone to neoadjuvant chemotherapy in triple-negative breast cancer after ≥4 years of follow-up: BrighTNess, a randomized phase 3 trial. Ann Oncol;32(suppl_5): S407–S446. doi:10.1016/annonc/annonc687