Drug combo yields ‘excellent’ survival outcomes in HER2+/HR- early breast cancer

A de-escalated neoadjuvant regimen of pertuzumab and trastuzumab plus paclitaxel leads to high pathologic complete response (pCR) rates and survival in people with hormone receptor-negative, HER2-positive early breast cancer (HER2+/HR-). According to Dr. Nadia Harbeck (PhD), who presented results from the WSG (West German Study Group)-ADAPT Her2+/HR- trial at the 2021 ASCO conference, this is “the first time shown … in a prospective multicenter trial, both excellent pCR and survival in patients treated by de-escalated 12-week neoadjuvant weekly paclitaxel and dual HER2 blockage, irrespective of additional chemotherapy use.” Dr. Harbeck is head of the Breast Center at the University of Munich in Germany. WSG-ADAPT Her2+/HR- was a randomized trial of 134 patients with HER2 positive hormone receptor negative early breast cancer. The primary endpoint of the study was pCR while the secondary endpoints were invasive disease-free survival and overall survival. They were randomized into one of two groups. The first group, group A, received 12 weeks of dual HER2 blockade with trastuzumab and pertuzumab every three weeks. The second group, group B received 12 times weekly paclitaxel plus dual HER2 blockade. There was a randomization ratio of five to one which resulted in 92 patients in arm A and 42 patients in arm B. Read: Active surveillance reduces unnecessary treatment in prostate cancer About a third of the patients were under 50 years of age. About 40% of the tumours were node positive. Almost 90% of the tumours were grade-3, and close to 90% were HER2-3 plus. Median follow-up was 16 months. Surgery was performed within three weeks after completion of the 12 weeks of the study therapy. “If non-pCR was confirmed histologically, centres could also add standard neoadjuvant therapy before surgery,” she said. But if pCR after 12 weeks of study therapy occurred in patients, stopping additional chemotherapy was allowed at the discretion of investigators. All patients underwent a three-week biopsy before cycle two of therapy to assess for early responses. “Early response was defined as either a relative K67 decrease greater or equal to 30% vs baseline. Or low cellularity— that is, less than 500 invasive tumor cells,” she said. In the neoadjuvant chemotherapy-free arm (group A), 34.4% of all patients had pCR breast lymph nodes, while over 90% had pCR in group B (weekly paclitaxel). The respective rates for total pCR without an in situ component were 24.4% and 78.6% respectively, she said. However, because chemotherapy after pCR was optional, it was omitted in 29% of the patients in group A and 79% of patients in group B (the paclitaxel plus dual HER2 blockade regimen), a significant difference. Invasive disease-free survival by five years was 87% in arm A where trastuzumab and pertuzumab alone were given for 12 weeks. And 98% in group B which included the paclitaxel. Distance disease-free survival were similar between the groups at 92% in group A and 98% in group B. Overall survival at five years was 94% in group A and 98% in group B. The results also highlighted the importance of pCR status on invasive disease-free survival. In group A “we see that pCR after de-escalated therapy is meaningful for patient outcome. In patients with pCR after 12 weeks of dual HER2 blockade alone, five-year invasive disease-free survival was 98% corresponding to one event – and just as good as that in the paclitaxel-containing in arm B,” said. Dr. Harbeck. “Patients with non-pCR after 12 weeks of dual HER2 blockade alone had 10 events corresponding to a five-year invasive disease-free survival of only 83%. Five-year invasive disease-free survival in arm B was excellent overall with 98%,” she said. Dr. Harbeck noted that in addition to the WSG-ADAPT Her2+/HR- trial, other de-escalation trials with similar concepts are ongoing, notably COMPASS and DECRESCENDO. “These findings are highly encouraging, particularly since the majority of patients in this study had stage two or three disease, and outside of this study, they would be subjected to a more aggressive and toxic standard-of-care regimen,” said Dr. Jane Lowe Meisel, an ASCO Expert in breast cancer and an associate professor of Hematology and Medical Oncology at Emory University School of Medicine, and was not involved in the study. “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. The study also sheds more light on the potential for chemo-free regimens for certain subsets of the HER2+ population,” she said.

Drug combo yields ‘excellent’ survival outcomes in HER2+/HR- early breast cancer

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