Rudolf Maibach and Heidi Roschitzki, IBCSG Coordinating Center, Bern
Figure 1. Lectures during the IBCSG Annual Meeting in the imperial setting of the Kaiserlounge of the Parkhotel Schönbrunn.
COOPERATIVE GROUPS: IBCSG
Figure 2. Friendly exchange during the IBCSG Dinner: Barry Gusterson (right) with Rich Gelber (middle) and Brian Leyland-Jones (left).
spective. Nadia Bianco, a young POSITIVE investigator at the top recruiting site in Milan, shared her experience in the field of patients’ recruitment. The huge participa-tion and productive discussion was very welcome!
The Data Managers Workshop, organized by the IBCSG Data Management Center is also a tradition of the IBCSG Annual Meeting, and very helpful for site person-nel involved in IBCSG trials.
The Scientific Program on Sunday started with the Early Trial Development Session presented by Marco Colleoni and Angelo Di Leo, co-chairs of the Scientific Executive Committee.
The Scientific Session served to look back on the achieve-ments of the past year and to present an overview of the ongoing projects by the respective trial chairs.
Guy Jérusalem gave an overview of the group’s impres-sive scientific achievements during 2016. He particularly stressed the prestigious publication record with 17 peer-reviewed manuscripts with an impact factor sum of 173.
This year’s social event started with a nostalgic city tour through Vienna which ended in picturesque «Heuriger», a traditional Austrian Tavern. Rolf Stahel, President of the Foundation Council, warmly welcomed all attendees and thanked Marianne Wenger for the perfect organization of the Meeting.
Thank you and Farewell to Professor Barry Gusterson
The IBCSG Annual Meeting was also the time to say goodbye and thank you to Barry Gusterson, who has been an active member of IBCSG for over 30 years and was Director of the Central Pathology Review in London and Glasgow. His motivation came from the vision to bring the IBCSG into a leader position in «Precision Medicine in Breast Cancer», a goal which has actually been achieved under his leadership.
We are deeply grateful for the over 30 years of Barry’s commitment and wish him a wonderful retirement.
CLINICAL TRIALS
IBCSG 48-14/BIG 8-13 POSITIVE
The best available evidence suggests that pregnancy after breast cancer therapy does not negatively impact disease outcome and is safe for the offspring, but no definitive information is available to recommend a safe interval from breast cancer diagnosis to pregnancy. The POSITIVE tri-al investigates endocrine therapy interruption to enable conception for young women between 18 and 42 years of age with endocrine responsive early breast cancer who
received adjuvant endocrine therapy for 18 to 30 months and wish to attempt pregnancy.
The main objectives are:
• to assess the risk of breast cancer relapse associated with temporary interruption of endocrine therapy to permit pregnancy;
• to evaluate factors associated with pregnancy success after interruption of endocrine therapy.
The trial also evaluates biologic correlates of pregnancy and disease outcome.
A psycho-oncological companion study evaluating psy-chological distress, fertility concerns and decisional con-flict in young women who participate in POSITIVE has been developed and is being activated in sites interested and capable to conduct it.
A total of 500 patients are planned to be recruited into the trial from centers worldwide in approximately 4 years. In Switzerland, 13 planned sites are open with 15 patients enroled overall so far.
As of 30 March 2017, the trial has been activated in 113 sites from 15 countries (Switzerland-SAKK, Australia, Italy, Belgium, Spain-SOLTI, Greece-HORG, Slovenia, USA-Alliance, Canada-CTG, Japan-JBCRG, Portugal-SOLTI, Netherlands, Hungary, Ireland-CTI and Norway-NBCG) with an accrual of 120 patients overall in the main trial and 67 patients in the psycho-oncological com-panion study. The trial will be activated in five additional countries in the near future (Serbia, South Korea, Israel, Austria and France).
To date, 24 patients have been pregnant and six healthy babies have been delivered, two of them in Switzerland!
IBCSG 45-13 PANACEA
There is a clear need to develop new therapeutic agents for patients presenting with HER2-overexpressing or HER2-positive metastatic breast cancer. A significant amount of preclinical and correlative clinical data sug-gests that HER2-positive breast cancer could be ame-nable to immunotherapeutic approaches. PANACEA is a phase Ib/II trial evaluating the efficacy of the combi-nation of pembrolizumab and trastuzumab in patients with HER2-positive metastatic breast cancers who have progressed on prior trastuzumab-based therapy. The main objective is to determine if a monoclonal antibody targeted against PD-1, a T-cell negative regulator, can reverse trastuzumab resistance in patients previously progressing on trastuzumab.
Six patients were enrolled in the phase IB of the trial that served to determine the dose of pembrolizumab recommended for the subsequent phase II part. A first cohort of 40 patients with PD-L1 expressing tumor was then treated in the phase II. With amendment 1, it was decided to also study a cohort of 15 patients with PD-L1 negative tumors. Enrolment into this cohort has now stopped.
The trial is conducted in the 11 institutions from Austria, Australia, France, Belgium and Italy who form the Immu-notherapy Task Force of the Breast International Group (BIG).
IBCSG 53-14 PYTHIA
This is an international, multicenter, prospective single arm phase II biomarker discovery clinical trial. The pri-mary objective is to assess the association of PFS with gene mutations, gene copy number aberrations and gene signa-tures. Eligible patients are post-menopausal women with hormone receptor positive, HER2-negative metastatic or locally relapsed breast cancer whose disease has pro-gressed after prior adjuvant endocrine therapy or one line of systemic treatment, i.e., endocrine treatment or che-motherapy, administered for metastatic disease. The trial is included in the AURORA program conducted by the Breast International Group (BIG), an international study aiming to collect and characterize biological samples, in-cluding metastatic tissue, from patients with advanced breast cancer. Detailed molecular information, as well as functional image data for a subset of patients, will be available to identify putative biomarkers of response to the trial regimen.
PYTHIA was originally planned as a randomized, place-bo-controlled trial comparing the experimental combina-tion of palbociclib plus fulvestrant with a control of ful-vestrant plus placebo. The very promising results of the PALOMA-1 and PALOMA-3 trials prompted IBCSG and BIG to abandon the control arm and to conduct the trial with one single arm. The strength of the trial lies in the translational research available because all patients are in-cluded in the AURORA program. Two gene signatures with potential predictive utility in terms of sensitivity to CDK4/6 blockade, one developed at the Université libre de Bruxelles and one from the Translational Research Unit at the Hospital of Prato, Italy (RBsig), will be evaluated as well. Baseline levels of activity of TK1 as well as early changes in TK1 expression levels measured during and after one cycle of therapy will also be studied. In addition, a sub-study with paired FDG-PET imaging is carried out in Belgian sites only.
The trial is being conducted at several sites in Belgium, Italy and the United Kingdom.
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tive breast cancer patients. Chemotherapy may need to be stopped due to lack of tolerability, lack of efficacy or pa-tient preference through subjective symptom assessment.
Time to treatment failure has been chosen as primary end-point. It is a composite endpoint combining all feasibility aspects of a treatment and is defined as time from the date of randomization to the date when the final dose of trial treatment is administered. It is therefore uniquely suited to the research question of the current trial.
The trial will be conducted at approximately 25 sites in Italy and is currently under activation.
IBCSG 54-16 METEORA-II
In the first-line treatment of patients with HER2 nega-tive advanced or metastatic breast cancer, various chemo-therapy regimens can be used including taxanes, which are among the most active agents in this setting. Single agent response rates range from 20 to 50%. However, eventually all patients will progress with a median time to progression of 5 to 7 months. Results from multicenter phase II trials have yielded a median time to progression for weekly paclitaxel in metastatic breast cancer patients in the range of 4.7-4.9 months.
Recently a single arm phase II trial conducted in Istituto Europeo di Oncologia in Milan (IEO) investigated a so-called metronomic oral chemotherapy with cyclophos-phamide plus capecitabine and vinorelbine in metastatic breast cancer. Patients received vinorelbine 40 mg orally on days 1, 3 and 5 every week, cyclophosphamide 50 mg daily and capecitabine 500 mg 3 times a day. This regime was called VEX. The goal was to deliver a regimen which is tolerable over a prolonged time period.
Given the promising activity and the good tolerability of the VEX regimen, the aim of METEORA-II is to inves-tigate whether the VEX schedule may improve efficacy and tolerability as compared to standard paclitaxel treat-ment in advanced or metastatic ER-positive/HER-2
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Correspondence:
Rudolf Maibach, PhD IBCSG Coordinating Center Effingerstrasse 40
CH-3008 Bern
rudolf.maibach@ibcsg.org www.ibcsg.org