Another option for HR+ /HER-2 negative pts who failed hormonal therapies, caution to toxicity though esp neutropenia and diarrhea, no OS data yet, will be interesting to know if it worth the adverse events at this stage of disease.
Hormone receptor–positive (HR+) human epidermal growth factor receptor 2–negative (HER2–) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer.
In this global, randomized, phase III study, SG was compared with physician’s choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in endocrine-resistant, chemotherapy-treated HR+/HER2– locally recurrent inoperable or metastatic breast cancer. The primary end point was progression-free survival (PFS) by blinded independent central review.
Patients were randomly assigned to receive SG (n = 272) or chemotherapy (n = 271). The median age was 56 years, 95% had visceral metastases, and 99% had a prior cyclin-dependent kinase 4/6 inhibitor, with three median lines of chemotherapy for advanced disease. Primary end point was met with a 34% reduction in risk of progression or death (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P = .0003]). The median PFS was 5.5 months (95% CI, 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy; the PFS at 6 and 12 months was 46% (95% CI, 39 to 53) v 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) v 7% (95% CI, 3 to 14), respectively. Median overall survival (first planned interim analysis) was not yet mature (hazard ratio, 0.84; P = .14). Key grade ≥ 3 treatment-related adverse events (SG v chemotherapy) were neutropenia (51% v 38%) and diarrhea (9% v 1%).
SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR+/HER2– advanced breast cancer and limited treatment options.
Another trial with neoadjuvant immunotherapy showing improved results over chemotherapy alone. (12% higher PCR 48% vs 36%).
Dato-DXd is now approved in HR+, HER2-neg, metastatic breast cancer after prior therapy with endocrine-based therapy and chemotherapy. There was an impressive reduction in the risk of death or progression with an HR of 0.63. Watch out for ocular and pulmonary toxicity. HER2-ultra low testing will be burdensome but must be done for drug approval.
TD beat chemotherapy after failure of hormonal therapy in HER-2 low and ultra low. Wait for the indication.
MammaPrint did not predict distant recurrence, but it did predict patients who may benefit from extended hormonal therapy. We do have breast index, so now we have options. Breast index can predict the possibility of recurrence though by helping to determine the level of risk.
This study confirms what we saw in initial reports showing the addition of pembro increasing the rate of ypathological complete response (ypCR’s) in the neoadjuvant setting for triple-negative breast cancer (TNBC). New data shows a 5% improvement (87 vs 82%) in overall survival (OS) with the quadruplet. Higher gains but at higher cost of toxicity. The fact that adjuvant intraosseous (IO) does not seem to improve outcomes, but neoadjuvant chemo+IO does show intact tumor-immune interactions to create maximum treatment effectiveness is most likely real. Of note, this seems mostly independent of programmed death-ligand 1 (PDL1) status.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
