medwireNews: A de-escalated neoadjuvant regimen of pertuzumab and trastuzumab plus paclitaxel leads to “excellent” pathologic complete response (pCR) rates and survival in people with hormone receptor-negative, HER2-positive early breast cancer, phase 2 study findings indicate.
Speaking at the 2021 ASCO Annual Meeting, Nadia Harbeck, from Ludwig Maximilian University of Munich in Germany, reported that the WSG-ADAPT HR-/HER2+ trial also showed that chemotherapy-free regimens “are promising in highly sensitive tumors with early response.”
The trial included 134 women who were randomly assigned to receive four cycles of dual HER2 blockade with pertuzumab (840 mg loading dose then 420 mg every 3 weeks) plus trastuzumab (8 mg/kg loading dose then 6 mg/kg every 3 weeks), either with (n=42) or without (n=92) weekly paclitaxel 80 mg/m2.
Approximately 60% of participants had tumors that were stage cT2–T4 and approximately 40% were node-positive. All women underwent surgery within 3 weeks of the end of neoadjuvant therapy.
Harbeck said previous analyses showed that the group who received dual HER2 blockade plus paclitaxel had a pCR rate of 90.5% at 12 weeks, while those who did not receive paclitaxel had a rate of 34.4%, a difference that led to the early termination of the trial.
The current analysis focused on survival outcomes and revealed that there was no significant difference in 5-year invasive disease-free-survival (DFS) rates between the people who did and did not receive paclitaxel, at 98% versus 87%.
There was also no significant difference between the two arms in 5-year distant DFS rates (98 vs 92%) or 5-year overall survival rates (98 vs 94%).
However, further analysis indicated that having a pCR, irrespective of study arm, was associated with a significantly higher 5-year invasive DFS rate, at 98%, compared with 82% among people with no pCR, corresponding to a hazard ratio of 0.14.
Similar results were observed when only considering the group that did not receive paclitaxel, with 5-year invasive DFS rates of 98% versus 83% in those with versus without a pCR.
Within this chemotherapy-free group, the researchers looked for biomarkers that might identify individuals unlikely to respond to HER2 blockade alone. They found that early pCR rates (measured by biopsy at 3 weeks) varied by subtype. Specifically, there were no early pCRs among participants with low HER2 expression and/or a basal-like subtype, and these tumors, plus those without an early response, were subsequently described as “non-sensitive” to HER2-blockade alone (33.7% of 92).
Invasive DFS rates at 5 years were 79% in people with non-sensitive tumors compared with 93% among those with other tumor types.
In a statement to the press, Jane Lowe Meisel, an ASCO Expert in breast cancer, said: “These findings are highly encouraging, particularly since the majority of patients in this study had stage 2 or 3 disease, and outside of this study, they would be subjected to a more aggressive and toxic standard-of-care regimen.
“This study indicates that we may be able to use early pathological complete response as a predictor of good outcomes, and that achieving this might reasonably allow for further treatment de-escalation.”
She concluded that “[t]he study also sheds more light on the potential for chemo-free regimens for certain subsets of the HER2+ population.”
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