Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: A survival analysis of the ADAPT-TP trial suggests that it may be possible to use early pathological complete response (pCR) as a means of identifying early-stage, triple-positive breast cancer patients who may be able to avoid chemotherapy.
The study findings were presented by Nadia Harbeck, from the Ludwig Maximilians University Hospital- Grosshadern, Munich in Germany, at the ESMO Virtual Congress 2020.
She explained that the phase II multicentre study included 375 patients with hormone receptor-positive, HER2-positive early breast cancer who were randomly assigned to receive a 12-week course of neoadjuvant trastuzumab emtansine (T-DM1) 3.6 mg/kg alone (n=119) or alongside endocrine therapy (ET; n=127), or trastuzumab plus ET (n=128).
The presenter reminded delegates that the primary endpoint of the study of pCR at time of the 12-week follow-up biopsy was achieved by 41.0% of the T-DM1-only arm and 41.5% of the T-DM-1 plus ET arm versus 15.1% of the trastuzumab plus ET arm. Omission of further chemotherapy was allowed for patients who achieved pCR at 12 weeks.
After a minimum follow-up of 5 years, and a median of 60.5 months, the time to event analysis showed that a pCR was significantly associated with better disease-free survival (DFS), with 5-year rates of 92.7% versus 82.7% among those without a pCR. The 10% difference between the groups is “clinically highly meaningful”, Harbeck said.
This difference translated into improvements in the overall patient outcomes, she continued, noting that there have been three deaths so far among patients who achieved a pCR versus 16 deaths among those who did not.
The 5-year DFS rates were comparable between the study arms, at 88.9% for patients given T-DM1, 85.3% for those given T-DM1 plus ET and 84.6% for patients receiving trastuzumab plus ET.
“The fact that this substantial pCR difference between the T-DM1 arms and the trastuzumab endocrine therapy arm did not translate into a difference in outcome is most likely due to the additional administration of standard chemotherapy in all patients without pCR and in the majority, that is 65%, of patients with pCR”, the presenter commented.
Distant DFS between the groups was also similar, with 5-year rates of 91.6%, 92.3% and 88.9%, respectively, and there were corresponding overall survival 5-year rates of 97.2%, 96.4% and 96.3%, the presenter said.
And DFS after pCR did not differ significantly between patients who did and did not receive chemotherapy.
Nadia Harbeck suggested these “excellent” survival rates in the study “may serve as a basis for future prospective trials addressing omission of [chemotherapy] overtreatment in carefully selected patients with HER2-positive early breast cancer.”
“The fact that in all pCR patients only three deaths have occurred is a very strong clinical indication that the pCR achieved without systemic therapy in ADAPT-[TP] can also be [a] durable pCR regarding patient outcome”, the presenter commented.
She concluded that “ADAPT-TP demonstrates [the] feasibility and safety of early pCR-guided trials for therapy de-escalation in HER2-positive early breast cancer.”
Harbeck N, Nitz U, Christgen M, et al. De-escalated neoadjuvant T-DM1 with or without endocrine therapy (ET) vs trastuzumab+ET in early HR+/HER2+ breast cancer (BC): ADAPT-TP survival results. Ann Oncol 2020; 31 (Suppl 4): S1142–S1215. DOI:10.1016/annonc/annonc325.
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