No Benefit to Routine Use of Platinum Agents After Neoadjuvant Chemo in Triple-Negative Breast Cancer

By Marilynn Larkin

June 18, 2021

NEW YORK (Reuters Health) - In patients with triple-negative breast cancer (TNBC) and residual invasive disease (RD), there is no benefit and more toxicity when platinum agents are given after neoadjuvant chemotherapy (NAC), researchers say.

"Based on pre-clinical models and preliminary clinical data supporting the use of platinum agents in the TNBC basal-subtype, EA1131 (researchers) hypothesized that invasive disease-free survival (iDFS) would not be inferior but improved in patients with at least 1 cm of residual basal-subtype TNBC...treated with adjuvant platinum compared to capecitabine," Dr. Ingrid Mayer of Vanderbilt University in Nashville told Reuters Health by email.

"Unfortunately," she said, "results show that platinum agents do not improve outcomes in patients with TNBC RD post-NAC, regardless of intrinsic subtype, and are associated with more severe toxicity when compared to capecitabine."

"Furthermore, participants had a much lower than expected three-year iDFS regardless of study treatment, highlighting the need for better therapies in this high-risk population," she noted.

"As such," she said, "these findings have an immediate impact in clinical practice, as they should discourage the adjuvant use of platinum agents in patients with residual TNBC after NAC outside of a clinical trial."

As reported in the Journal of Clinical Oncology and at the ASCO 2021 Virtual Meeting, Dr. Mayer and colleagues randomly assigned patients with clinical stage II or III TNBC with at least 1 cm RD in the breast post-NAC to receive platinum (carboplatin or cisplatin) once every three weeks for four cycles or capecitabine 14 out of 21 days every three weeks for six cycles.

The study had a noninferiority design a with superiority alternative, assuming a four-year iDFS of 67% with capecitabine.

Four hundred and ten of the planned 775 participants were randomly assigned to the platinum or capecitabine regimens between 2015-2021. The median age at randomization was 52 and 72% were white. The interval between surgery and random assignment was a median of 115 days.

After a median follow-up of 20 months and 120 iDFS events (61% with full information) in the 78% of patients with basal subtype TNBC, the three-year iDFS was 42% for platinum versus 49% for capecitabine.

Further, grade 3 and 4 toxicities were more common with the platinum agents.

The Data and Safety Monitoring Committee recommended stopping the trial at that point, as it was unlikely that further follow-up would show noninferiority or superiority of platinum

Dr. Mayer said, "For now, the use of platinum agents in unselected patients with residual TNBC after NAC remains investigational and capecitabine remains the standard therapy."

Dr. Adam Brufsky, Associate Division Chief for the Division of Hematology/Oncology at the University of Pittsburgh School of Medicine and Medical Director of the Magee-Women's Cancer Program, told Reuters Health by phone, "I think a lot of us who were using carboplatin are going to think a little bit differently about it and be more selective in the patient populations we're going to use it with, rather than using it with everyone."

"Current guidelines say the use of carboplatin is optional, at the physician's discretion, and it will probably stay that way," he said.

"Some physicians still believe quite strongly that they will keep using it in this setting, because some studies show a higher pathologic complete response when carboplatin is used in the neoadjuvant setting," he said. "Others believe there's a little bit of benefit to people with genetically associated breast cancer."

"But I think that after seeing these data, people will be unlikely to use it without thinking, and will be more selective and a bit cautious about who they use it with going forward," Dr. Brufsky concluded.

SOURCE: Journal of Clinical Oncology, online June 6, 2021