While the autumn started showing itself in some parts of Europe, the sun was shining in the city of Gaudi which was home to more than 28,000 attendees for the ESMO 2019 annual congress. For one week, Barcelona was flooded with top-quality science and ambitious visions that will shape the future of cancer therapies.
While the autumn started showing itself in some parts of Europe, the sun was shining in the city of Gaudi which was home to more than 28,000 attendees for the ESMO 2019 annual congress. For one week, Barcelona was flooded with top-quality science and ambitious visions that will shape the future of cancer therapies.
The opening ceremony (lead by Oncode Investigator Emile Voest) marked the tagline of ESMO 2019 'Translating science into better cancer patient care'. While the results of potentially practice changing Phase III trials from global pharma drew attention at the conference, European biotech and academic research brought cutting edge advances to the table. Oncode Investigators and Dutch academic researchers have taken the global stage during the ESMO annual congress 2019 with two impactful genomic guided studies, in multidisciplinary presentations on rational targeted therapy combinations and excellence in translational cancer research models.
Clinical setting
Two genomics-centered trials in the Netherlands driven by Oncode Investigators - the Center for Personalized Cancer Treatment (CPCT-02) and Drug Rediscovery Protocol (DRUP) - showed the potential of tumour genomic features to guide treatment for advanced cancer patients. Presented by Emile Voest, the DRUP trial reported results for 215 Dutch patients with advanced cancer without any further treatment options. These patients were matched based on their genomic features and given a medicine that was registered for another cancer type. Clinical benefit was observed in 34% of 215 patients, showing a previously unnoticed benefit of broad tumor genome sequencing.
As part of the same session, Oncode Investigator Edwin Cuppen shared findings from the CPCT-02 trial, another prospective effort done through the Center for Personalized Cancer Treatment. In this pan-cancer whole genome analysis, 2520 tumors were sequenced, and in 62% of all patients genetic variants indicated actionable targets. The analysis of study results helps our understanding of tumor features such as that TMB is indifferent in primary tumor and metastasized tumors or that the tumor cell heterogeneity decreases in metastatic lesions.
One of the spotlights of the Presidential Symposium series were the PARP inhibitors. Based on the results of several studies, PARP inhibitors (PARPi) expand their role in treatment landscape beyond ovarian cancer and BRCA mutation bearing tumors and are shifting to the first line of therapy. However, this broad expansion comes with a need of biomarker-based patient selection.
Extremely promising results point out a shift in neoadjuvant therapy for triple negative breast cancer (TNBC) in the near future with PD-1 checkpoint blockade regimen leading to higher pathological complete response rates. Meanwhile, robust evidence shown in the MONARCH 2 and MONALEESA-3 trials supports the addition of CDK6/7 inhibitors to endocrine therapy resulting in longer survival in Hormone receptor positive (HR+) breast cancer patients.
Christian Blank presented the results of OpACIN trial conducted at Netherlands Cancer Institute in collaboration with the Royal Marsden Hospital. The results indicated a 20% increase in 3 year relapse free survival upon treatment with ipilimumab (PD-1) plus nivolumab (CTLA-4) combination for stage III metastatic melanoma. OpACIN was the first trial investigating neoadjuvant IPI + NIVO in patients with macroscopic stage III melanoma, thus having the longest follow-up. Oncode Investigator Ton Schumacher was also involved in the study.
Biomarker, Biomarker, Biomarker
Biomarkers were certainly amongst the most popular words of the ESMO 2019 congress and are key to rational, precision-medicine therapies and successful clinical results. Beyond typical mutated genes (BRCA1/2) and overexpressed proteins (HER2, PD-L1), Tumor Mutational Burden (TMB), Minimal residual disease (MRD), Microsatellite Instability (MSI) and their spatio-temporal variations were extensively discussed.
Early datasets from two analyses reported conflicting results regarding the role of TMB as biomarker for pembrolizumab plus chemotherapy in NSCLC and differences in comparison with monotherapy only. Results indicated the need for identifying other molecular subtypes in NSCLC.
Pros and cons of liquid biopsy (ctDNA) versus tissue biopsies were also discussed. Take-home messages were that liquid biopsies are advantageous for certain measurements including repetitive sampling, but tissue biopsies are still a necessity for tumor heterogeneity, tumor microenvironment and wide screening of mutations and signatures. Overall, there is a discordance between the liquid vs tissue biopsies and not every biomarker works for every tissue, also changes might occur throughout the duration of the disease and treatment.
Translational Research
Biomarker guided precision medicine and developments in cell therapies were amongst the highlights of the translational cancer research in Barcelona. Friday afternoon kicked off with a showcase of functional genomic approaches for the rational and immune cell treatment combinations in a session chaired by Oncode Investigator Daniel Peeper and Joseph Tabernero. More than 50 drugs for 30 genomic alterations are already on the market and there is an increasing trend in genetically guided therapies. However, speakers called for action on the harmonization of the reporting, scalability and identifying the correlation for mutation-drug in different tissues. In a parallel educational session, Oncode Investigator Jos Jonkers discussed the pros and cons of the preclinical models and imaging for guiding clinical decisions. Jos Jonkers’ research utilized genetically engineered mouse models (GEMM) and functional genomics (tumor derived organoids/cell lines) to predict PARPi resistance.
ESMO2019 has given us food for thought: Ever growing importance of biomarkers, broader applications of IO and PARPi, and changing practice of phase III studies only possible in a collaborative ecosystem with industry and academic stakeholders. Oncode researchers continue to be influential in shaping the future of cancer therapies. Get in touch with our valorization team if you would like to partner with Oncode research or if you are an Oncode researcher looking for industry partner in the next ESMO, BIO, AACR meetings. See you at the next event!