New findings have provided more evidence that omitting carboplatin from standard neoadjuvant therapy in HER2-positive early breast cancer can improve tolerability without compromising short-term efficacy, supporting a potential de-escalation approach.

In the phase 3 neoCARHP randomized noninferiority trial, the neoadjuvant triple regimen of a taxane plus trastuzumab and pertuzumab (THP) was associated with comparable pathologic complete response rates compared with the standard regimen of THP plus carboplatin (TCHP) but with significantly fewer high-grade adverse events in patients with HER2-positive stage II or III breast cancer.

The neoCARHP trial results were the focus of a presentation at Miami  Breast Cancer Conference 2026 and were also published in the Journal of Clinical Oncology earlier this year.

Based on this trial and others, “the times may be ripe to omit carboplatin for the neoadjuvant treatment of HER2+ breast cancer,” Paolo Tarantino, MD, PhD, with the breast oncology program, Dana-Farber Brigham Cancer Center in Boston, wrote in an editorial in JCO.

Kathy Miller, MD, who wasn’t involved in the trial, agreed. There have now been a couple of trials comparing the same regimen with and without carboplatin, explained Miller, who co-leads the breast cancer program at Indiana University Health, Indianapolis.

“In all, carboplatin adds very little, if anything,” she said, adding that she “only adds carboplatin in the fittest patients with really bad extensive disease.”

Safely Skip Carboplatin?

Carboplatin-containing regimens such as TCHP remain a standard neoadjuvant treatment option in National Comprehensive Cancer Network guidelines. However, the regimens come with significant toxicities.

In the neoCARHP trial, researchers aimed to evaluate whether carboplatin could be safely omitted in HER2-positive breast cancer without compromising efficacy.

The researchers, led by Hong-Fei Gao, MD, with the Cancer Center at Guangdong Provincial People’s Hospital, Guangzhou, China, enrolled 774 women with previously untreated stage II-III HER2-positive breast cancer. Patients were randomized (1:1) to receive six cycles of either TCHP or THP every 3 weeks, with the taxane selected by investigators. Overall, 766 patients were included in the modified intention-to-treat population.

The primary endpoint — pathologic complete response in the breast and axilla in the modified intention-to-treat population — was achieved in 64% of patients in the THP group and 66% in the TCHP group, meeting the predefined criterion for noninferiority (odds ratio, 0.93; 95% CI, 0.69 to 1.25; P for noninferiority = .0089).

In the per-protocol population, pathologic complete response rates were identical in the two groups (68.5%). Subgroup analyses showed similar efficacy across hormone receptor (HR)-positive and HR-negative disease. Pathologic complete response rates were 56% with THP and 59% with TCHP in HR-positive disease, and about 78% in both groups in HR-negative tumors.

Grade 3-4 adverse events occurred in 20.7% of patients in the THP group compared with 34.6% in the TCHP group, and serious adverse events were reported in about 1.3% vs 4.7%.

Hematologic toxicities were notably reduced with THP, including lower rates of neutropenia (6.8% vs 16.4%), leukopenia (5.5% vs 14.8%), and thrombocytopenia (0.3% vs 4% grade ≥ 3). Treatment discontinuation and dose reductions were also less frequent in the carboplatin-free group.

“These findings suggest that omitting carboplatin may serve as an alternative neoadjuvant strategy” in this setting, the study authors concluded.

The Broader Landscape

Overall, the neoCARHP findings “add to a growing body of evidence suggesting that, for patients with low- and moderate-risk HER2-positive breast cancer, carboplatin may be safely omitted from the neoadjuvant regimen without compromising outcomes at surgery,” Tarantino explained in his editorial.

Tarantino noted that the research to date suggests that about half of patients with stage II or III HER2-positive disease achieve a pathologic complete response on 4 cycles of THP, and that response can increase to more than 60% with 6 cycles of THP.

 The phase 3 HELEN-006 trial, for instance, directly compared a de-escalated regimen of weekly nab-paclitaxel plus trastuzumab and pertuzumab with the standard docetaxel-carboplatin backbone over six cycles, and found that the carboplatin-free regimen was associated with a higher pathologic complete response rate (66% vs 58%) and a lower incidence of grade 3 or 4 adverse events.

Tarantino did note several caveats to this evidence, including that long-term survival data are still immature, most trials have focused on stage II (not stage III) disease, optimal regimen details (drug, schedule, duration) are still unclear, and evidence mainly comes from Chinese patients.

Tarantino also pointed out that emerging therapies may further shape treatment strategies, and that the treatment landscape for HER2-positive early breast cancer is shifting toward tailoring therapy based on tumor biology, immune environment, and early treatment response.

“While we reap the products of a decade of de-escalation trials, the challenge ahead is to ensure that de-escalation is not merely less therapy, but truly tailored therapy, guided by the tumor’s biology, its immune background, and its dynamic response to treatment,” he wrote.

The neoCARHP trial had no commercial funding. Author disclosures are available with the original articles.