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Dr Donatienne Taylor, a medical oncologist at the Clinique Sainte-Elisabeth CHU UCL Namur, reported on the late break abstract session at SABCS 2023.  She reported five presentations, three on immunotherapy, one on a novel HER2-driven antibody and the latest on the ADAPTcycle study.

The first study reported is the KEYNOTE 522 trial that was also presented at the last ESMO, showing a notable 9% advancement in EFS through immunotherapy in early-stage triple-negative breast cancer. Today’s presentation focused on EFS results categorized by subgroups. Notably, Peter Schmidt reported outstanding outcomes within the stage II disease subgroup, revealing a substantial 10% improvement in EFS. These findings serve to strengthen the current clinical recommendation for immunotherapy in triple-negative early breast cancer, reaffirming its pivotal role in contemporary treatment paradigms.

The second immunotherapy trial that Dr Taylor reported was the APTneo Michelangelo trial. This randomised phase 3 trial focused on exploring the efficacy of atezolizumab in combination with standard chemotherapy in high-risk early and locally advanced HER2+ breast cancer. In Arm A the standard trastuzumab plus pertuzumab (HP) and chemotherapy (CT) regimen was administered for six cycles. Arm B included chemotherapy plus atezolizumab, further subdivided into B1 and B2, with B1 featuring an anthracycline-based regimen and B2 comprising the HPCT plus atezolizumab. The incorporation of an anthracycline aimed to assess its potential synergy with immunotherapy due to its known immunogenic properties. The reported pCR rates, a secondary endpoint, exhibited a numerical advantage with immunotherapy, particularly in combination with anthracycline. However, statistical significance was not achieved, underscoring the uncertainty about the necessity of immunotherapy in this context until EFS results are disclosed. Notably, the regimens showed no unexpected toxicities, alleviating concerns in this regard.

The third trial discussed involves a primarily Australian study (BCT1902/IBCSG 61-20 Neo-N) that investigated the use of nivolumab in combination with chemotherapy in early-stage triple-negative breast cancer. The trial focused on patients with stage I and stage II TNBC, exploring the concept of a lead-in nivolumab strategy before initiating chemotherapy. This approach aimed to stimulate immunogenicity and potentially allow for the de-escalation of chemotherapy by administering a shorter course. The study enrolled slightly over 100 patients in a non-comparative manner, with the primary endpoint being pCR. The results demonstrated a notably high pCR rate, exceeding 50% for all patients, regardless of the administration sequence of nivolumab. Importantly, the trial did not reveal a significant advantage in terms of pCR rates between the groups receiving nivolumab as a lead-in versus concurrently with chemotherapy. Despite this, the overall findings are encouraging, especially considering that the patients received a shorter and less intensive chemotherapy regimen than the standard approach for this population.

The next late-breaking abstract was a phase 2A trial on zanidatamab in combination with palbociclib and fulvestrant for patients with HER2+/HR+ metastatic breast cancer. Zanidatamab is a novel HER2 antibody that targets two specific extra-domain areas of HER2. The trial enrolled a heavily treated patient population with an average of four prior lines of treatment in the metastatic setting. The results revealed compelling findings, particularly considering the advanced stage of the disease. The six-month PFS rate was reported at 67%, and the median PFS reached 12 months in this previously treated cohort. The study’s outcomes are noteworthy because they explore the combination of HER2-targeting agents with endocrine sensitivity in later lines of treatment. Typically, such combinations are not extensively studied in advanced stages of the disease. The promising results from this trial suggest that this combination strategy may have a meaningful impact on disease control and progression in patients with HER2+/HR+ metastatic breast cancer who have exhausted multiple prior lines of therapy.

The last late-breaking abstract provided results from the ADAPTcycle trial, a complex German study aimed at refining the selection criteria for chemotherapy in early-stage HR+ breast cancer. The trial leverages endocrine treatment sensitivity, particularly using Ki-67 levels after two to four weeks of endocrine therapy. If Ki-67 decreases to less than 10, it is deemed endocrine-sensitive. By combining endocrine treatment response and the recurrence score, the trial seeks to better identify patients who may or may not benefit from chemotherapy. In premenopausal women, the trial demonstrated that the endocrine treatment response dramatically varies whether tamoxifen only or an AI and OFS are used. The combination of an AI and OFS resulted in almost 80% endocrine treatment sensitivity, resembling the levels seen in postmenopausal women. This finding is noteworthy as it suggests that the choice of endocrine therapy can significantly impact treatment response. While the study provides valuable insights into Ki-67 response based on the type of endocrine treatment, the ultimate question of whether this translates into improved EFS outcomes requires further follow-up.

References:

Schmid P. et al., Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer: Updated event-free survival results from the phase 3 KEYNOTE-522 study –  SABCS 2023, #LB01-01

Gianni L. et al., Pathologic complete response (pCR) of neoadjuvant therapy with or without atezolizumab in HER2-positive, early high-risk and locally advanced breast cancer: APTneo Michelangelo randomized trial – SABCS 2023, #LB01-02

Zdenkowski N. et al., Randomized Phase II Study of Neoadjuvant Nivolumab (N) 2 week lead-in followed by 12 weeks of concurrent N+carboplatin plus paclitaxel (CbP) vs concurrent N+CbP in Triple Negative Breast Cancer (TNBC): (BCT1902/IBCSG 61-20 Neo-N) – SABCS 2023, #LB01-03

Escriva-de-Romani S. et al., Primary results from a phase 2a study of zanidatamab (zani) + palbociclib (palbo) + fulvestrant (fulv) in HER2+/HR+ metastatic breast cancer (mBC) – SABCS 2023, #LB01-04

Gluz O. et al., Impact of age and ovarian function suppression (OFS) on endocrine response to short preoperative endocrine therapy (ET): Results from the multicenter ADAPTcycle trial (n=4,334) – SABCS 2023, #LB01-05