HER2+ Breast Cancer: Skipping Carboplatin May Safely Reduce Toxicity

For patients with HER2-positive breast cancer, the addition of carboplatin to a taxane and dual HER2-targeted therapy has been a longtime cornerstone of neoadjuvant, or presurgical, treatment.

But findings from the phase 3 neoCARHP trial and the phase 2 EA1181 biomarker analysis presented at the 43^rd Annual Miami Breast Cancer Conferece suggest that carboplatin may be safely omitted in select patients without compromising pathologic complete response (pCR) rates.

“Selecting the best neoadjuvant therapy [is] very important [because] neoadjuvant treatment also reduces the amount of surgery and post-surgery radiation that patient might need,” said Dr. Priyanka Sharma, professor of medicine, University of Kansas Medical Center in Kansas City, during a presentation at the conference, adding that results from the neoCARHP trial and the EA1181 biomarker analysis signal a shift toward "right-sizing" therapy to reduce toxicity while maintaining high efficacy.

The NeoCARHP Trial: Challenging the Carboplatin Mandate

The neoCARHP trial was a multicenter, randomized phase 3 study designed to evaluate whether a carboplatin-free regimen (THP: taxane, Herceptin [trastuzumab] and Perjeta [pertuzumab]) is non-inferior to the standard carboplatin-containing regimen in patients with stage 2 to 3 HER2-positive breast cancer. The study randomly assigned 774 patients to receive either six cycles of THP or the standard carboplatin-containing regimen every three weeks.

In the overall population, the pCR rate was 64% for the THP group compared to 66% for the carboplatin-containing group. A subgroup analysis revealed that pCR rates were identical (78%) in both arms for patients with hormone receptor (HR)–negative disease, while those with HR-positive disease saw a slight numerical difference (56% versus 59%, respectively).

While efficacy was comparable, the safety profiles differed markedly. The addition of carboplatin led to significantly higher rates of grade 3 (severe)/4 (life-threatening) hematological adverse effects. Specifically, neutropenia occurred in 16.4% of the carboplatin-containing arm compared to 6.8% in the THP arm. Thrombocytopenia and anemia were also more prevalent in the carboplatin group (4.2% vs 0.3%, respectively; and 6.6% vs 2.1%). Furthermore, grade 3/4 creatinine increases were noted only in the carboplatin-containing group (1.3% versus 0%, respectively).

The neoCARHP results suggest that extending this carboplatin-free treatment to six cycles (18 weeks) can push pCR rates into the 60% range, rivaling more intensive regimens. However, Sharma noted that event-free survival (EFS), disease-free survival, overall survival (OS) and biomarker data are awaited.

Biomarkers and "Right-Sizing" Therapy

The EA1181 study (CompassHER2 pCR) further supported treatment de-escalation by identifying which patients are most likely to achieve pCR with shorter, carboplatin-free therapy. In this trial, 2,141 patients received 12 weeks of THP. Multivariable analysis confirmed that lower estrogen receptor (ER) expression and higher HER2 expression (immunohistochemistry [IHC] 3+) were strong predictors of pCR.

Additionally, the HER2DX pCR score, a genomic signature, was independently predictive of pCR across multiple studies. High HER2DX scores identify patients who may achieve pCR with dual HER2 blockade alone or limited chemotherapy, while low scores may signal a need for more intensive multi-agent regimens.

Expert Interpretation on Carboplatin Omission

While the neoCARHP results are compelling, Sharma urged a nuanced application in clinical practice. The trial exclusively enrolled a Chinese population, and nearly half of the patients received Abraxane (nab-paclitaxel), which is not currently FDA-approved for this specific neoadjuvant indication. Furthermore, the study population was predominantly lower risk, with only 8% of patients having stage 3 disease in related de-escalation trials like CompassHER2 (EA1181).

She added that providers should consider that, while carboplatin omission appears safe for clinical T1-2 or N0-1 disease with HER2 IHC 3+ status, its role may still be relevant for patients with higher-risk stage 3 disease or those with IHC 2+ disease, where pCR rates were numerically lower. Long-term outcomes, including EFS and OS from neoCARHP, are still pending and will be critical to confirming that pCR non-inferiority translates to survival parity.

References

1. “Optimal neoadjuvant chemotherapy, who needs carboplatin for HER2+ disease?” by Dr. Priyanka Sharma, presented at: 43rd Annual Miami Breast Cancer Conference; March 5-8, 2026; Miami, Florida.
2. “Neoadjuvant Taxane Plus Trastuzumab and Pertuzumab With or Without Carboplatin in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: The Randomized Noninferiority Phase III neoCARHP Trial,” by Dr. Hong-Fei Gao, et al., J Clin Oncol.
3. “Predicting pathologic complete response (pCR) from clinicopathologic variables and HER2DX genomic test in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): Secondary results from the EA1181/CompassHER2 pCR trial” by Nadine M. Tung et al., J Clin Oncol.

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