Esmo Open

Several phase III trials on immune checkpoint inhibitor therapy in non-small cell lung cancer were recently published and changed the clinical practice Here, non-small cell lung cancer has to be categorized first according to the presence of activating mutations and second according to the programmed cell death ligand 1 (PDL1) expression. Approximately 25% of patients present with a driver mutation and should be treated with tyrosine kinase inhibitors as the first line treatment strategy for metastatic non-small cell lung cancer. Approximately 75% of patients do not present with a driver mutation and should be treated according to the presence of PDL1 expression. Patients with high PDL1 (≥ 50% of tumor cells) expression are candidates for immune checkpoint inhibitor monotherapy, although a combination with chemotherapy can be suggested in patients with high tumor load and fast progressing disease. Patients with intermediate (1-49% of tumor cells) PDL1 expression are on the other hand candidates for the comb

Epigenetic biomarkers are emerging across tumor types in cancer research. Aberrant DNA methylation in tumors results in silencing of distinct genes. This modification is very stable and therefore can reliably be assessed and used as a diagnostic but also prognostic biomarker. Recently, DNA methylation was validated as an additional diagnostic biomarker in brain tumors. Here, the methylation profile allowed precise clinical diagnosis associated with the survival prognosis. Therefore, the addition of DNA methylation profiles to routine diagnostic assessment in cancer diagnosis might be promising to ensure accurate diagnosis and support treatment decisions. Further, predictive epigenetic biomarkers were identified as MGMT methylation was repeatably shown to associate with response to alkylating chemotherapy. Several current research efforts are concentrating on the identification of new diagnostic as well as predictive biomarkers in various types of cancer. This podcast with Professor Gerda Egger (Department of

Immunotherapy has been approved for several indications in Oncology, resulting in an increasing number of physicians that use it to treat their patients. In this podcast, Teresa Amaral, member of the ESMO YOC, interviews Professor John Haanen (Head of the Division of Medical Oncology and Staff Scientist in the Division of Immunology; Professor of Translational Immunotherapy of Cancer at Leiden University Medical Centre, the Netherlands) on the topic: “Questions asked in everyday practice: Immune Checkpoint Inhibitors”. Currently, there is no consensus about how long should we treat patients with immunotherapy and the optimal duration might also be different considering the tumor type (e.g. melanoma, NSCLC). In some patients, stopping early due to adverse events doesn’t seem to be detrimental, but the follow-up time is still short to make definitive assumptions. When treating a patient with a previous autoimmune disease, several aspects need to be considered, namely, which type of immunosuppression is the pati

Although highly successful in other entities, immune checkpoint inhibition has so far only shown limited efficacy in an unselected population of colorectal cancer patients. The particular composition of the inflammatory microenvironment of colorectal cancer, characterized by a low density of tumor-infiltrating-lymphocytes and no PDL1 expression on the tumor cells, might explain this resistance. Indeed, colorectal cancer with microsatellite instability responds much better to immune checkpoint inhibitors and present with a much higher infiltration with T-cells. Dense infiltration with tumor-associated macrophages at the invasion margin is a further characteristic of the inflammatory microenvironment in colorectal cancer potentially causing the limited response to immune checkpoint inhibitors. Interestingly, PDL1 expression can be frequently observed on these tumor-associated macrophages at the invasion margin, which potentially reduce the infiltration with T cells. Interfering with this population of myeloid c

Colorectal cancer has a strong interaction with the immune system as underlined by the high prognostic impact of tumor infiltrating lymphocytes in the tumor core as well as the infiltration margin in the localized setting. However in the metastatic scenario the vast majority of these tumors - the 95% lacking deficiencies in the missmatch repair sustem- demonstrated to be immune-elusive. The new therapeutic bispecific anti-CEA anti CD3 antidobody CEA-TCB is therefore a new, promising immune modulating therapy currently evaluated in clinical studies in colorectal cancer. The CEA-TCB has a 2-to-1 binding ratio, with one domain of the antibody binding directly to CD3 on T cells while the remaining two binding domains simultaneously bind to CEA molecules on the tumor cells. The CEA-TCB induces T-cell­ engagement and activation, with T-cell proliferation at the site of activation. Two phase 1 trials with CEA-TCB have been presented this year, one as a single-drug trial, the other in combination with the PD-L1 inhib

In the last decade, we have seen a significant change in the therapeutic landscape for advanced melanoma. Recently, results from two trials evaluating immunotherapy and targeted therapy in the adjuvant setting (completely resected stage III/IV) were published. In this podcast, Teresa Amaral, member of the ESMO YOC, talks with Professor Jeffrey Weber, Professor of Oncology and Deputy Director of the Laura and Isaac Perlmutter Cancer Center, about the recent developments in adjuvant therapies for patients with melanoma. Professor Weber also gives some insight on this data's impact on the treatment of real-world patients. Currently, there is enough evidence to support adjuvant treatment in patients with resected Stage IIIB/C-IV melanoma. As for Stage II patients, this option should be considered in some selected cases (e.g. T ≥ 4mm with the presence of ulceration). In both of the above-mentioned trials, patients were treated for a maximum of 12 months. Although a shorter treatment duration (e.g. 6 months) mig

In this podcast, Editor Anna Berghoff speaks to Professor Eric Tartour (Department of Immunology; Hôpital Européen Georges Pompidou) about new therapeutic targets in the inflammatory microenvironment. The introduction of immune checkpoint inhibitors introduced a new era of oncology. The CTLA4 or PD1/PDL1 axis targeting immune checkpoint inhibitors have shown remarkable and long lasting responses in a variety of tumor types, Here, the biology of immune checkpoint inhibitors is outlined including the main site of action for the different immune checkpoint inhibitor types. Further, other possible immune checkpoints like LAG3 and other cells types including macrophages and NK cells as future directions for immune modulating therapies are discussed. Combination approaches including immune checkpoint inhibitors and chemotherapy or radiotherapy are currently investigated for their synergistic efficacy and preliminary data has shown promising results. Read the Abstract on the ESMO Open website: http://esmoopen.bmj.c

Immune Checkpoint inhibitors have become an important treatment option in patients with metastatic lung cancer. This podcast gives an overview on the current evidence of immune checkpoint inhibitors in patients with non-small cell lung cancer. Based on the phase III data, patients with PDL1 expression >50% are candidates for 1st line pembrolizumab if there are no contraindications. Currently, PDL1 expression as assessed by immunohistochemistry is the most validated biomarker although other biomarkers including mutational load, neo-antigen presence or tumor infiltrating lymphocytes are currently under investigation. Importantly, the side effect profile of immune checkpoint inhibitors does not differ in lung cancer patients. Studies are currently investigating the value of immune checkpoint inhibitors for patients with small cell lung cancer. Several currently on-going studies are investigating the combination of chemo-/radiotherapy and immune checkpoint inhibitors in patients with lung cancer. Read the abstr

Several alumni of the European Society for Medical Oncology (ESMO) Leaders Generation Programme introduce the scope, aims and goals of the program. The ESMO Leaders Generation Programme was designed to shape the future of the oncology profession as well as the future of ESMO. This exciting and intensive course has been specifically created for young oncologists to provide them a specific training needed for future leadership. Covered topics include ESMO and the world of oncology as well as the development of personal skills especially in the areas of communication, leadership and career development. All qualified medical or clinical oncologists working in Europe who are ESMO members and aged between 31 and 45 years are invited to apply for the program. The course is divided into two parts and provides a variety of interactive training as well as mentoring by experts in the field of oncology. Applications can be filled out on the ESMO homepage. The alumni give detailed insights on their most valuable ESMO Lead

Professor Marco Merlano, Oncology Department Santa Croce e Carle, General Hospital, Italy, is the leading author of the ESMO Open article ‘Heterogeneity of colon cancer: from bench to bedside’, summarised in this podcast. Abstract The large bowel shows biomolecular, anatomical and bacterial changes that proceed from the proximal to the distal tract. These changes account for the different behaviour of colon cancers arising from the diverse sides of the colon–rectum as well as for the sensitivity to the therapy, including immunotherapy. The gut microbiota plays an important role in the modulation of the immune response and differs between the right colon cancer and the left colorectal cancer. The qualitative and quantitative difference of the commensal bacteria between the right side and the left side induces epigenetic changes in the intestinal epithelial cells as well as in the resident immune population. The second player in the pathological homeostasis of colorectal cancer is the differences of the genet

In this podcast new, practice-changing research in gastrointestinal (GI) cancer is considered. Clinical trials focusing on immunotherapies presented at the recent ASCO Gastrointestinal Cancers Symposium in San Francisco are discussed. Highlights include reports of the ONO-4538 study, in which pretreated gastric cancer patients were randomized to receive either nivolumab or best supportive care, and of the CheckMate 040 study in which pretreated patients with hepatocellular carcinoma received nivolumab. Nivolumab is also assessed in the CheckMate 142 which considered patients with DNA mismatch repair deficient/microsatellite instability high metastatic colorectal cancer. Other new treatment options and combinations with immunotherapy are briefly considered, but the author suggests that it is too early to draw conclusions from these preliminary data. Emergent side effects from immunotherapy trials in GI cancer are also discussed. In closing the author considers developments in immunotherapy of GI canc

Elżbieta Senkus, Medical University of Gdansk, Department of Oncology and Radiotherapy, Gdańsk, Poland, (elsenkus@gumed.edu.pl) presents an overview of new therapies on the horizon for breast cancer in terms of data presented at the ESMO Congress, ASCO, and the San Antonio Breast Cancer Symposium. In the adjuvant setting, results from the MINDACT trial, which evaluated genomic versus clinical assessment for risk stratification, are described. Data on the role of anthracyclines in adjuvant chemotherapy is also discussed. In HER2-positive patients, dual HER2-targeted therapy was investigated in the KRISTINE study, and studies on the duration of adjuvant endocrine therapy in advanced breast cancer are also considered. Other ongoing studies in this population and the luminal population are also briefly mentioned. In the metastatic setting, the PALOMA-2 and MONALEESA-2 studies assessed the addition of CDK4/6 inhibitors to standard treatments. Results of the MONARCH 1 trial, evaluating a CDK4/6 inhibitor as a si

In this podcast a new biological insight in brain tumors is discussed by Frank Winkler, DKFZ, CCU Neurooncology, Heidelberg, Germany (f.winkler@dkfz.de). The author’s group has identified the existence of a tumor cell network in incurable gliomas which facilitates multicellular communication and exchange of small molecules between single tumor cells. The tumor cells that are integrated in this network, around 50% of cells according to studies in mouse models and patient samples, appear to be protected from the effects of radiotherapy and possibly also chemotherapy, which may explain how such tumors develop resistance to therapies and why patients relapse after treatment. An overview of ideas that are being investigated preclinically to therapeutically target this network of tumor cells is given. These include approaches to disrupt the network, such as obstructing cellular communication with gap junction blockers and targeting the neurodevelopmental pathways required to form the networks. Conversely, metho

A critical review of the highlights in breast cancer research from the American Society of Clinical Oncology (ASCO) meeting 2016, held in June 2016 in Chicago, is presented in this podcast by Fatima Cardoso, Breast Unit, Champalimaud Clinical Center, Lisbon, Portugal (fatimacardoso@fundacaochampalimaud.pt). Considering the most interesting and practice-changing studies reported at the meeting, in the advanced breast cancer setting several important confirmatory studies on the use of CDK inhibitors, and studies on using data on estrogen receptor mutations to guide choices of endocrine therapy are discussed. The PHEREXA trial, in which a combination trastuzumab and pertuzumab was studied in the advanced setting is also considered. In the early breast cancer setting, the KRISTINE and ADAPT studies evaluated the potential of dual blockade in HER2-positive tumors. In HER2-negative early breast cancer several trials are also discussed with respect to types of adjuvant chemotherapy. The results of the MA.17R t

These highlights are presented by Marco Merlano, Department of Medical Oncology, Santa Croce General Hospital, Cuneo, Italy,(mcmerlano@gmail.com). A critical review of the head and neck cancer research highlights of the American Society of Clinical Oncology (ASCO) meeting 2016, held in June 2016 in Chicago, is presented in this podcast. Considering the most interesting and practice-changing trials reported at the meeting, the key trial comparing gemcitabine plus cisplatin against 5-FU plus cisplatin in the treatment of nasopharyngeal carcinoma is highlighted. The GORTEC2007-02 trial comparing induction docetaxel/platinum/ 5-FU followed by cetuximab-radiotherapy against concurrent chemo-radiotherapy for N2b/c-N3 non operated stage III-IV squamous cell cancer of the head and neck is also discussed. An overview of the research reported using immunotherapy in head and neck cancer is also given, considering maturing data and particularly in relapsing patients, where response rates, though low, are better than

The highlights are presented by Rolf A. Stahel, Universitätsspital Zürich, Onkologie, Zürich, Switzerland (rolf.stahel@usz.ch). A critical review of the highlights of the European Lung Cancer Conference (ELCC) 2016, held in April 2016 in Geneva, is presented in this podcast. Considering the most interesting and practice-changing trials reported at the meeting, the key trial on the use of osimertinib in patients with non-small cell lung cancer (NSCLC) with EGFR harbouring the T790M mutation who had progressed on first line tyrosine-kinase inhibitors (TKIs) was highlighted. The meeting also featured interesting studies on testing for the T790M mutation and highlighted the potential of liquid biopsies. Two areas of potentially valuable biomarker development were stressed: biomarkers in oncogenic-driven NSCLC, and, more controversially, immunotherapy-related biomarkers. New treatment strategies were highlighted by the presentation of the Heine H. Hansen Award to Professor Suresh Senan (Amsterdam) whose work

These highlights are presented by Emile Voest, The Netherlands Cancer Institute - Molecular Oncology, Amsterdam, Netherlands (e.voest@nki.nl). The author reviews the recently published article “Facilitating a Culture of Responsible and Effective Sharing of Cancer Genome Data” (Nat Med. 2016 May 5;22(5):464-71 - http://goo.gl/O3DRMf.) considering why data sharing is important and explaining the obstacles and problems involved. The need to identify common bioinformatics pipelines and resolve outstanding legal, ethical and technical issues are highlighted. Particular attention is given to emerging issues around informed consent and the handling of electronic patient records. There is a real need to address all these issues now on multiple levels in order to fulfil the promise of personalised medicine. The author further considers the work of the Global Alliance for Genomics and Health across cancer, rare diseases and in the emerging field of infectious diseases genomics. Finally, the potential impact of ca

A critical review of the highlights of the ESMO Symposium on Signalling Pathways in Cancer 2016, held March 2016 in partnership with the European Association of Cancer Research, is presented in this podcast. The meeting addressed developments in personalized medicine associated with the HER/EGFR family. Key subjects discussed were the bases of the mechanisms of signal transduction and primary and secondary resistance to EGFR-inhibiting drugs, and the emergence of better characterized subtypes of common tumors such as colorectal cancer, breast cancer, lung cancer and gastric cancer, and new utilities to effect these characterizations. Findings to consider include the increasing importance of tumor heterogeneity; the understanding that not all cells in a tumor have the same mutation may help develop new kinase inhibitors and new strategies. Further, data suggest that maintaining inhibition of the signaling process, even in the face of secondary resistance, can prolong clinical benefit. There is a need to de

A critical review of key studies from the ASCO 2016 Gastrointestinal Cancers Symposium, held January 2016, is presented in this podcast. A number of tumor areas, including gastric, esophageal and colorectal cancers, are considered with an emphasis on recent developments in immunotherapy. Studies reviewed include the CheckMate-032 trial, which assessed the activity of the anti-PD-1 antibody nivolumab in patients with advanced gastric or gastroesophageal junction cancer, the KEYNOTE-028 trial, for which results of the esophageal carcinoma cohort treated with pembrolizumab were presented, and updated results of a trial considering PD-1 blockade in mismatch repair deficient non-colorectal gastrointestinal cancers. Biomarkers are further considered in the Mavericc trial which sought to stratify metastatic colorectal cancer patients by ERCC1 in order to predict their response to platinum-based treatments. Neoadjuvant therapy was considered with the results of a study, from the Polish Colorectal Study Group, u

A critical review on the practice changing studies presented at the San Antonio Breast Cancer Symposium, held December 2015, is presented in this podcast. A number of areas, including neoadjuvant and adjuvant treatment, treatment of metastatic disease and the emergence of new biomarkers are addressed. Trials discussed include the WSG-ADAPT HER2+/HR+ phase II trial, which assessed 12-weeks of neoadjuvant TDM1 with or without endocrine therapy vs. trastuzumab+endocrine therapy in HER2-positive hormone-receptor-positive early breast cancer, the CREATE-X study, which assessed adjuvant capecitabine in patients with HER2-negative pathologic residual invasive disease after neoadjuvant chemotherapy, and the TH3RESA study, which investigated trastuzumab emtansine use in patients with previously treated HER2-positive metastatic breast cancer. Further, studies on new promising biomarkers such as the prognostic value of circulating tumor cells in follow up of early breast cancer patients after adjuvant chemotherapy are