Advertisement

ADAPT: Survival Outcomes After Neoadjuvant Dual HER2 Therapy for HR-Negative, HER2-Positive Breast Cancer


Advertisement
Get Permission

The first overall survival analysis of the WSG-ADAPT HR-/HER2+ study, which evaluated neoadjuvant therapy in patients with hormone receptor (HR)-negative, HER2-positive breast cancer, showed that treatment with pertuzumab and trastuzumab plus paclitaxel—or the chemotherapy-free regimen of pertuzumab/trastuzumab alone—can yield excellent survival outcomes. These findings were presented by Nadia Harbeck, MD, PhD, and colleagues during the 2021 ASCO Annual Meeting (Abstract 503). 

“For the first time, we have shown both excellent pathologic complete response rates and survival in patients treated by de-escalated 12-week neoadjuvant weekly paclitaxel and dual HER2 blockade, irrespective of further chemotherapy use, in a prospective multicenter study,” said Dr. Harbeck, Head of the Breast Center and Chair for Conservative Oncology at the University of Munich. 


For the first time, we have shown both excellent pathologic complete response rates and survival in patients treated by de-escalated 12-week neoadjuvant weekly paclitaxel and dual HER2 blockade, irrespective of further chemotherapy use, in a prospective multicenter study.
— Nadia Harbeck, MD, PhD

Tweet this quote

In addition, the achievement of a pathologic complete response after only 12 weeks of neoadjuvant pertuzumab/trastuzumab and paclitaxel was strongly associated with improved outcomes—only one such patient developed distant disease—and could potentially serve as a predictive clinical marker for further treatment de-escalation or escalation, she said.

The West Germany Study Group had previously reported that 12 weeks of pertuzumab/trastuzumab plus paclitaxel yielded a pathologic complete response rate of 90%, whereas the chemotherapy-free pertuzumab/trastuzumab regimen led to a 34% rate. Dr. Harbeck presented the survival data at the 2021 ASCO Annual Meeting.  

After a median follow-up of 5 years, no significant differences between study arms emerged in disease-free survival, distant disease–free survival or overall survival. Only 13 invasive disease–free survival events (7 were distant) were observed in the whole intent-to-treat population, Dr. Harbeck reported.

About the Study

As Dr. Harbeck noted, the optimal use of de-escalated neoadjuvant regimens—particularly chemotherapy-free therapies—in HER2-positive early breast cancer has been unclear, as survival data for such approaches has been limited. The prospective multicenter WSG-ADAPT HR-/HER2+ phase II trial evaluated this question.  

The study enrolled 134 patients with cT1-cT4c, cN0-3 HR-negative, HER2-positive early breast cancer, of whom 60% had tumors that were cT2-4; 42% were clinically node-positive.

Patients were randomly assigned to four cycles of pertuzumab (840 mg → 420 mg) plus trastuzumab (8 mg/kg → 6 mg/kg) every 3 weeks for four cycles (n = 92) or the same plus paclitaxel (80 mg/m2) weekly for 12 cycles (n = 42); patients underwent surgery within 3 weeks of treatment completion. If a pathologic complete response was achieved after 12 weeks of study treatment, additional chemotherapy could be omitted at the investigator’s discretion.

The trial’s objective was to compare pathologic complete response rates in patients in the pertuzumab/trastuzumab/paclitaxel arm to early responders in the pertuzumab/trastuzumab arm (defined as low cellularity and/or Ki67 decrease > 30% after 3 weeks). The primary endpoint was pathologic complete response (ypT0/is/ypN0).

KEY POINTS

  • The first overall survival analysis of the WSG-ADAPT HR-/HER2+ trial has been reported, following up on previous findings of pathologic complete response rates of 90% with pertuzumab/trastuzumab plus paclitaxel and 34% with pertuzumab/trastuzumab alone.
  • Patients received 12 weeks of pertuzumab/trastuzumab plus paclitaxel or dual HER2 blockade alone.
  • The study shows that treatment can often be de-escalated in this population without compromising long-term outcomes.

Survival Outcomes

After a median follow-up of about 5 years, the invasive disease–free survival rate was 98% with the triplet and 87% with dual HER2 blockade alone (hazard ratio [HR] = 0.32; P = .144). Distant disease–free survival was 98% and 92%, respectively (HR = 0.34; P = .313) and overall survival was 98% and 94% (HR = 0.41; P = .422).

The achievement of a pathologic complete response (vs not) after the 12-week study treatment was strongly associated with improved invasive disease–free survival at 5 years, irrespective of study arm: 98% vs 82% (HR = 0.14; P = .011).

The investigators examined the benefit of neoadjuvant chemotherapy–free dual HER2 blockade alone according to cancer subtype, HER2 status by immunohistochemistry (IHC), and early response to treatment. They saw no pathologic complete responses in patients who had low HER2 expression (IHC 1+/2+ and fluorescence in situ hybridization–positive) and/or the basal-like subtype by the PAM50 assay. Low HER2 expression and/or lack of early response were strongly associated with worse distant disease–free survival and invasive disease–free survival, she added.

“Chemotherapy-free regimens are promising in highly sensitive tumors with early response. Further investigations of chemotherapy-free regimens may need to be focused on selected patients only, such as those with high HER2 expression and non–basal-like tumors,” Dr. Harbeck said. “De-escalation trials with similar concepts—including COMPASS and DECRESCENDO—are ongoing.”

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
Advertisement

Advertisement



Advertisement