Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer
TD beat chemotherapy after failure of hormonal therapy in HER-2 low and ultra low. Wait for the indication.
This is a 10-year follow-up of the ShortHER study using nine weeks vs. 12 months of adjuvant trastuzumab in HR+ non-metastatic breast cancer. With long-term follow-up, non-inferiority could not be claimed statistically. Still, the DFS/OS results are identical in those patients with N0-N3 disease, while those with N4 disease seemed to have a significant difference favoring 12 months of therapy, suggesting that volume/burden of disease drives the margin of benefit in adjuvant trastuzumab therapy.
We present the final analysis of the phase III noninferiority, randomized ShortHER trial comparing 9 weeks versus 1 year of adjuvant trastuzumab with chemotherapy in patients with human epidermal growth factor receptor 2–positive (HER2+) early breast cancer (BC). Women with HER2+ BC were randomly assigned to anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or 9-week trastuzumab (arm B, short). Here, we report the second coprimary end point overall survival (OS), updated disease-free survival (DFS), and outcomes according to hormone receptor status, age, and nodal status. At a median follow-up of 9 years, 10-year DFS is 77% versus 78% in the long versus short arm, respectively. Ten-year OS is 89% versus 88% in the long versus short arm, respectively. 10-year DFS rates in the long versus short arm according to nodal status are N0 81% versus 85%; N1-3 77% versus 79%; and N4+ 63% versus 53%. Ten-year OS rates in long versus short arm according to nodal status are N0 89% versus 95%%; N1-3 92% versus 89%; and N4+ 84% versus 64%. The updated analysis of the ShortHER trial shows that 1-year trastuzumab is the standard treatment for patients with HER2+ early BC as noninferiority cannot be claimed. However, numerically, the differences for the patients at low or intermediate risk (N0/N1-3) is negligible, while patients with N4+ have a clear benefit with 1-year trastuzumab.
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).
Well done study showing a 20% decrease in recurrence risk when using dose dense therapy [EC]/D compared to conventional dose [FEC]/D. Sometimes it is worth it to push.
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