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.
The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2–directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator’s choice of chemotherapy (ICC) in hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer.
Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS).
Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367). Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; P < .0001). Consistent PFS benefit was observed across subgroups. Although OS data were not mature, a trend favoring Dato-DXd was observed (HR, 0.84 [95% CI, 0.62 to 1.14]). The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% v 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC.
Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile, compared with ICC. Results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2‒ breast cancer who have received one to two previous lines of chemotherapy in this setting.
Another trial with neoadjuvant immunotherapy showing improved results over chemotherapy alone. (12% higher PCR 48% vs 36%).
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.
Adding Inavolisib to CKD4/6 inhibitor and AI improved progression-free survival (almost doubled 15 vs 7m) but toxicity was higher still in the single digits (hyperglycemia, diarrhea, stomatitis… all less than 6% G3/4).
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.
