Details of what works, and what doesn’t, in triple-negative breast cancer (TNBC) come from long-term follow-up of the phase 3 randomized BrighTNess trial.
The initial improvement that was seen in pathologic complete response (pCR) rates with the addition of carboplatin to paclitaxel and standard neoadjuvant chemotherapy translated into improved event-free survival (EFS) rates in patients with resectable TNBC more than 4 years after surgery.
The benefits of adding carboplatin to paclitaxel, followed by four cycles of AC (doxorubicin and cyclophosphamide) chemotherapy, were seen both in patients with germline BRCA mutations as well as those with wildtype BRCA.
The trial results also demonstrated, however, that there were no short- or long-term benefits to adding veliparib (ABT-888), a poly (ADP-ribose) polymerase (PARP) inhibitor, to the mix.
Although pCR and EFS rates were significantly improved with the combination of paclitaxel and carboplatin compared with paclitaxel alone, there were no significant differences when veliparib was added in either pCR, EFS, or overall survival (OS).
“These findings overall support the inclusion of carboplatin into neoadjuvant chemotherapy for stage 2 and 3 triple-negative breast cancer patients, regardless of germline BRCA status,” concluded lead author Sibylle Loibl, MD, PhD, chief executive officer and chair of the German Breast Group.
She presented the new data during an oral session at the virtual European Society for Medical Oncology (ESMO) Congress 2021.
The BrightNTess results show that “neoadjuvant carboplatin plus paclitaxel is superior to paclitaxel alone, with high pCR rates and benefit of event-free survival rates with manageable toxicity and no safety signals,” commented invited discussant Monica Arnedos, MD, PhD, head of the breast cancer research program at the Institut Bergonié in Bordeaux, France.
The findings also put to rest the notion that patients with germline BRCA mutations would not benefit from carboplatin treatment because of extreme sensitivity to standard neoadjuvant chemotherapy.
“The BrighTNess study says otherwise,” Arnedos said. “Today we’ve seen that the pCR improved event-free survival regardless of the germline BRCA mutated status, so BRCA-mutated germline patients require neoadjuvant carboplatin.”
The new data may lead to changes in breast cancer guidelines, she suggested.
Prior to these results, the evidence was that “platinum salts as neoadjuvant chemotherapy increased pCR rates in triple-negative breast cancer patients, but this was associated with more toxicity, and with higher rates of treatment discontinuation and dose reduction, without strong evidence of long-term benefit. This led to a lack of consensus to recommend platinum salts in this setting between the different breast cancer guidelines.”
The new BrighTNess data showed that the improved pCR rates translated into an EFS benefit in both platinum-containing groups of the trial, a finding that is consistent with the KEYNOTE-522 trial, which showed that adding pembrolizumab (Keytruda) to chemotherapy improved pCR in patients with early TNBC.
The BrighTNess results suggest that patients with high- or moderate-risk TNBC could be treated in the neoadjuvant setting with paclitaxel and carboplatin followed by standard chemotherapy concurrently with pembrolizumab, followed by surgery, and adjuvant therapy with pembrolizumab plus olaparib (Lynparza) for patients with germline BRCA mutations, or capecitabine for patients without mutations, Arnedos proposed.
BrighTNess Study Details
The BrighTNess trial involved 634 patients with previously untreated histologically or cytologically confirmed stage 2-3 TNBC who were candidates for potentially curative surgery and had a good performance status. They were randomly assigned to receive either paclitaxel plus carboplatin and veliparib, paclitaxel plus carboplatin only, or paclitaxel alone prior to four cycles of chemotherapy with doxorubicin and cyclophosphamide (AC).
Initial results, published in 2018 in The Lancet Oncology, showed that the addition of veliparib to carboplatin and paclitaxel improved pCR rates compared with paclitaxel alone, but not paclitaxel plus carboplatin. The trial data supported the addition of carboplatin to standard neoadjuvant chemotherapy, but not veliparib, the investigators stated at the time.
Now at the ESMO meeting, Loibl presented longer follow-up results.
After a median follow-up of 4.5 years, the hazard ratio (HR) for event-free survival with the paclitaxel/carboplatin/veliparib combination compared with paclitaxel alone was 0.63 (P = .016). In a post-hoc analysis, the adjusted HR was 0.57 (P = .018).
In a subgroup of 309 patients who had initial pCRs, the HR for EFS compared with patients without a pCR was 0.26 (P < .0001). Among patients with germline BRCA mutation, the HR for EFS for those who had a pCR was 0.14 (P = .0004), and among those with germline wildtype BRCA and a pCR the HR was 0.29 (P < .0001).
However, there were no significant differences in OS a median of 4.5 years after surgery.
An analysis of the frequency of myelodysplastic syndrome, acute myeloid leukemia, or other second primary malignancies also showed no significant differences between the groups, Loibl noted.
Although there were higher rates of hematologic malignancies with the addition of carboplatin, with or without veliparib, these adverse events did not compromise either treatment delivery of the benefits of carboplatin on the primary pCR endpoint, she added.
The BrighTNess trial was supported by AbbVie. Loibl has reported receiving grants and honoraria from AbbVie and others, including Medscape. Arnedos has reported receiving honoraria, travel grants, and/or research grants from AstraZeneca, Novartis, Pfizer, and Roche.
ESMO Congress 2021. Abstract 1190. Presented September 17, 2021.
Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.
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