EBCC-14 NEWS: Exciting new research to look out for at EBCC-14

The Chairs of Europe’s most exciting international breast cancer conference are looking forward to a fascinating and varied three days in Milan.

New results from cutting-edge clinical trials will, of course, be presented, but also innovative early/translational research, and issues around survivorship, metastatic breast cancer and making treatment for early breast cancer less toxic are high on the agenda too.

Chair of EBCC 14, Professor Michail Ignatiadis, Director of the Breast Medical Oncology Clinic at the Jules Bordet Institut, Université Libre de Bruxelles, Belgium, and Chair of the Breast Cancer Group of the EORTC, is looking forward to hearing about the final analysis of the ALEXANDRA/IMpassion030 phase III trial, in which he is an investigator.

“Neoadjuvant chemotherapy in combination with neoadjuvant and adjuvant administration of the PD1 inhibitor pembrolizumab is currently the standard of care for women with high-risk stage 2 and 3 triple-negative breast cancer (TNBC) based on the results of the pivotal Keynote 522 study. This study demonstrated that the addition of pembrolizumab resulted in a clinical meaningful, absolute improvement of 9% in event-free survival after a median follow-up of approximately five years.

“However, in several countries around the world, especially in community hospitals, TNBC patients with stage 2 disease are still being treated with surgery upfront. For these women, it was unknown whether adjuvant administration of PD1/PDL1 inhibitors could improve clinical outcome when added to adjuvant chemotherapy. ALEXANDRA/IMpassion030 is the only trial that investigated the role of the PDL1 inhibitor atezolizumab as adjuvant treatment in combination with anthracycline and taxane based chemotherapy in stage 2 and 3 TNBC patients.

“At EBCC-14, Professor Heather McArthur will present the results of the final analysis of this important trial. The ALEXANDRA/IMpassion030 trial contributes to an improved understanding about the optimal use of immunotherapy in patients with early TNBC,” he said.

Co-chair of EBCC 14, Dr Fiorita Poulakaki, Vice President of Europa Donna, the European Breast Cancer Coalition, as well as Head of the Breast Surgery Department, Athens Medical Center, Greece, said: “We expect a lot of interesting data to be presented about deescalating local regional treatment for early breast cancer. The four-year oncologic outcome of the MARI protocol, examining whether the omission of axillary lymph node dissection in cN2-3 breast cancer patients with an excellent response on primary systemic treatment is safe is one of them. Data on tailored axillary surgery after preoperative systemic therapy are lacking, especially in patients with extensive nodal disease and we expect to hear the results about the axillary recurrence rate, disease-free survival and overall survival of node-positive breast cancer patients with more than three suspicious axillary lymph nodes treated according to the MARI-protocol.

“On the topic of personalised treatment and considering young age as a risk factor for local relapse, the Young Boost trial (NCT00212121) investigated whether an increased boost dose could improve local control in young patients. Interesting data will be presented on the results of the ten-year primary analysis.

Survivorship issues are always of special value in a multidisciplinary conference such as EBCC. We eagerly look forward to PRE-ACT (Prediction of Radiotherapy side Effects using explainable AI for patient Communication and Treatment modification). This is an ongoing multidisciplinary European collaborative study with the goal of using artificial intelligence (AI) to predict long-term side effects (toxicity) from radiotherapy in breast cancer patients. The aim of PRE-ACT is to leverage its huge potential towards accurate toxicity prediction, and at the same time provide an easily understood explanation to support shared treatment decision-making between patient and physician.

Metastatic breast cancer issues are addressed at various level at EBCC14. The effects of exercise on fatigue and health-related quality of life (HRQoL) in patients with metastatic breast cancer (mBC) will be presented through the PREFERABLE-EFFECT study (NCT04120298), which was designed to assess effects of a nine-month supervised exercise programme in patients with mBC on fatigue, HRQoL and cancer- and treatment-related side effects. It will be very interesting to hear whether exercise effects are consistent across subgroups of patients,” she said.

Chair of the national organising committee, Professor Giuseppe Curigliano, Professor of Medical Oncology at the University of Milano and Head of the Division of Early Drug Development at the European Institute of Oncology, Milan, is looking forward to results from the KEYNOTE-756 phase III clinical trial.

“The management of hormone receptor positive (HR+) early breast cancer (EBC) is based on a risk-adapted optimisation strategy escalating adjuvant endocrine treatment (ET) with the addition of CDK4-6 inhibitors (CDK4-6i) in high-risk patients,” he said. “HR+ breast cancer has for long been considered non-immunogenic, and poorly responsive to neoadjuvant treatments, therefore not amenable to overall immunotherapy treatments with indications for neoadjuvant chemotherapy in high-risk HR+ EBC. However, in the last few years, HR+ breast cancer heterogeneity has emerged with variegated prognosis and immunogenicity. Recently, the results of two phase III, placebo-controlled randomised trials, shed new light on the use of immune checkpoint inhibitors (ICI) in high-risk HR+ EBC, questioning their current standard of care.

“The CheckMate 7FL and KEYNOTE-756 trials investigated, respectively, the addition of nivolumab and pembrolizumab to neoadjuvant anthracycline-taxane based chemotherapy and adjuvant ET. The ICI-arms of both trials achieved a higher statistically significant pathologic complete response (pCR) rate than placebo arm and met their primary endpoints. The high-risk target population of both trials was similar, identifying as grade (G)3, nodal (N) positive or T3-4 cN0 HR+ EBC, along with G2, oestrogen receptor (ER) low (1-10%) breast cancer only in the CheckMate trial.

“The selection of the population is in contrast with previous clinical trials. Notably, in the Giada trial, the sequential anthracycline-based neoadjuvant chemotherapy followed by nivolumab plus ET did not meet the pre-specified hypothesis of the trial (pCR of 25%) demonstrating a pCR of 16% in G3 LuminalB-like HR+ EBC. Biology appeared to drive the disease response, related to the intrinsic molecular subtypes, among which, basal-like tumours represented 50% of breast cancers with pCR. Among HR+ breast cancer, a small subset of immunoreactive tumours may benefit from ICI.

“Thus, we need to characterise the immune-vulnerability of HR+ breast cancer, including intrinsic characteristics of the tumour and its microenvironment, in order to understand immune-responsivity. No data are mature about the event-free survival, thus, if the pCR benefit will translate into an improvement in long-term outcome is still unknown. These results and long follow-up are awaited, because in HR+ breast cancer patients the late recurrences often affect their prognosis. Moreover, how this change of the neoadjuvant treatment can be integrated with the adjuvant CDK4-6i benefit remains unknown, targeting the same high-risk population.