However, adding the PARP inhibitor veliparib to carboplatin and neoadjuvant paclitaxel has no additional benefit.
"These findings support the inclusion of carboplatin in neoadjuvant chemotherapy for stage-II and -III triple negative breast cancer, irrespective of the germline BRCA status," Dr. Sibylle Loibl of the University of Frankfurt, Germany, said in presenting the data at the European Society for Medical Oncology (ESMO) Congress.
BrighTNess enrolled 634 women from 145 centers worldwide with previously untreated operable stage-II/III TNBC. They were randomly allocated to receive neoadjuvant paclitaxel, with added veliparib and carboplatin, added carboplatin, or added placebo, followed by doxorubicin and cyclophosphamide before surgery.
Initial findings from the trial showed that adding carboplatin, with or without veliparib, to paclitaxel led to significant improvement in pCR, the primary endpoint, with an acceptable safety profile.
At ESMO, Dr. Loibl reported data for the secondary endpoints of EFS and overall survival (OS), as well as second malignancies, after four or more years of follow-up.
At a median follow up of 4.5 years, EFS rates were 78.2% with the triplet of carboplatin, veliparib and paclitaxel, 79.3% with the doublet of carboplatin and paclitaxel, and 68.5% with paclitaxel alone.
While carboplatin, veliparib and paclitaxel was associated with a significantly higher hazard ratio (HR) for EFS than paclitaxel alone (HR, 0.63), the triplet was not superior to the doublet of carboplatin and paclitaxel (HR, 1.12). A post hoc analysis gave a HR for EFS of 0.57 with carboplatin plus paclitaxel versus paclitaxel alone, Dr. Loibl reported.
The mortality rate was low across all treatment groups: 10.0% in the carboplatin plus paclitaxel group, 12.0% in the carboplatin-paclitaxel-veliparib group and 13.9% in the paclitaxel alone group.
"After the 4.5 years of median follow up, overall survival was not statistically significantly different yet, but there was a trend for the carboplatin arms being superior to the non-carboplatin-containing arms," Dr. Loibl reported.
The regimens had manageable safety profiles with no increased risk of myelodysplastic syndromes, acute myeloid leukemia or other secondary malignancies, Dr. Loibl reported.
In an email to Reuters Health, Dr. Charles Shapiro, professor of medicine, hematology and medical oncology at Icahn School of Medicine at Mount Sinai and medical breast oncologist at the Tisch Cancer Center in New York, noted that after nearly five years of follow-up, the Brightness trial "establishes that carboplatin when added to weekly paclitaxel not only increases the complete pathological rate but also increases the event-free survival in triple-negative breast cancer."
"Whereas five prior randomized trials confirm that the addition of carboplatin to paclitaxel statistically significantly increases the pCR rate, few trials have sufficient follow-up to report early positive EFS results," noted Dr. Shapiro, who was not involved in the story.
Against expectations, adding veliparib failed to boost pCR rate, he said. "Perhaps, veliparib was the wrong PARP inhibitor as there are differences preclinically between the various PARP inhibitors."
"What is most exciting is use of a checkpoint inhibitor, pembrolizumab, in the neoadjuvant chemotherapy of TNBC (Keynote-522 trial). Unlike veliparib, pembrolizumab when added to paclitaxel and carboplatin during and after neoadjuvant chemotherapy, statistically significantly increased the pCR rate, and three-year EFS. What's more, these results were independent of PDL-1 status of the tumor," Dr. Shapiro noted.
The trial was sponsored by AbbVie. Several authors have disclosed financial relationships with the company.
SOURCE: https://bit.ly/3nNaaXt ESMO Congress, presented September 17, 2021.
By Megan Brooks
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