Some patients with breast cancer may now be able to safely and reasonably omit carboplatin therapy, especially those with lower-risk disease, according to data presented at the 43rd Annual Miami Breast Cancer Conference from the phase 3 neoCARHP trial (NCT04858529) and the phase 2 EA1181 biomarker analysis (NCT04266249).
Carboplatin, combined with a taxane, trastuzumab, and pertuzumab (TCbHP), is currently a preferred regimen in the National Comprehensive Cancer Network (NCCN) for stage II–III human epidermal growth factor receptor 2 (HER2)–positive breast cancer.
Pathologic complete response (pCR) rates were 64.1% in the carboplatin-omitted group (THP) (95% CI, 59.1–69.0%) and 65.9% in those treated with all four medications, TCbHP (95% CI, 60.9–70.6%).
In the THP group, omitting carboplatin resulted in significantly less toxicity, with grade 3 or 4 adverse events occurring in 20.7% of patients compared to 34.6% of those treated with TCbHP. Serious adverse events were less frequent with THP.
Two limitations of the neoCARHP trial are that the trial was conducted primarily in Chinese patients, which may affect generalizability, and long-term outcomes are still pending. Expanded patient populations and more data on event-free survival (EFS), disease-free survival, and overall survival (OS) will be critical to confirming that pCR non-inferiority translates to survival parity.
Regarding lower-risk disease, the EA1181 study (CompassHER2 pCR) of patients receiving THP found that lower estrogen receptor (ER) expression and higher HER2 expression (immunohistochemistry [IHC] 3+) were strong predictors of pCR. Additionally, high HER2DX scores may help identify which patients might achieve pCR with dual HER2 blockade alone or limited chemotherapy, thus lessening the toxicity burden.
These results continue to add to the remarkable advancements in precision medicine for breast cancer. By understanding the risks and benefits associated with omitting highly toxic regimens in favor of targeting higher-risk disease, clinicians can continue to offer patients the greatest benefit while lessening toxicities with a non-inferior regimen.