We evaluated the applicability of the scale and assessed the reasonableness of the generated scores in early breast cancer. Form 1 of the ESMO-MCBS v1.1 provided a generally robust tool for scoring of adjuvant breast cancer studies. Six shortcomings were identified including lack of information regarding acute and long-term toxicity, an inability to grade single arm de-escalation scales and limitations related to grading based on disease free survival (DFS).Read the paper on the ESMO Open website: http://dx.doi.org/10.1136/esmoopen-2020-000743

We evaluated the applicability of the scale and assessed the reasonableness of the generated scores in early breast cancer. Form 1 of the ESMO-MCBS v1.1 provided a generally robust tool for scoring of adjuvant breast cancer studies. Six shortcomings were identified including lack of information regarding acute and long-term toxicity, an inability to grade single arm de-escalation scales and limitations related to grading based on disease free survival (DFS). Read the paper on the ESMO Open website: <a href="http://dx.doi.org/10.1136/esmoopen-2020-000743" rel="nofollow" target="_blank">http://dx.doi.org/10.1136/esmoopen-2020-000743</a>

ESMO-Magnitude of Clinical Benefit Scale (V1.1) for early breast cancer therapies

Form 1 of the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) serves to grade therapies with curative intent. Form 1 provided very reasonable grading and expert field testers confirmed the reasonableness of generated scores. Exploratory toxicity evaluation and annotation was feasible but problematic given inconsistent toxicity reporting and limited results of late toxicity. Moreover, the experts identified the inability of crediting improved convenience in non-inferiority trials as a shortcoming. Future revisions of Form 1 of the ESMO-MCBS will be cognoscente of these findings.Read the paper on the ESMO Open website: http://dx.doi.org/10.1136/esmoopen-2020-000681

Form 1 of the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) serves to grade therapies with curative intent. Form 1 provided very reasonable grading and expert field testers confirmed the reasonableness of generated scores. Exploratory toxicity evaluation and annotation was feasible but problematic given inconsistent toxicity reporting and limited results of late toxicity. Moreover, the experts identified the inability of crediting improved convenience in non-inferiority trials as a shortcoming. Future revisions of Form 1 of the ESMO-MCBS will be cognoscente of these findings. Read the paper on the ESMO Open website: <a href="http://dx.doi.org/10.1136/esmoopen-2020-000681" rel="nofollow" target="_blank">http://dx.doi.org/10.1136/esmoopen-2020-000681</a>

ESMO-Magnitude of Clinical Benefit Scale of adjuvant colon cancer trials and meta-analyses

The therapeutic landscape in melanoma is evolving rapidly. In this podcast, Jonathan Lim (a member of the ESMO Young Oncologists Committee) interviews Dr Teresa Amaral (the current chair of the ESMO Young Oncologists Committee and an expert in melanoma) for an update on the current practice and advances in adjuvant and neoadjuvant therapies in melanoma. Dr Amaral summarises key practice-changing studies which have established the current recommendations in this field, including CheckMate 238, KEYNOTE 054, COMBI-AD, Combi-Neo, NeoCombi and opACIN-neo. We also deliberated on the toxicity profile of these therapies, and currently available evidence of neoadjuvant versus adjuvant therapies. Finally, we addressed how COVID-19 has affected the delivery of adjuvant and neoadjuvant therapies in patients with melanoma.Further reading:CheckMate 238 – https://doi.org/10.1056/NEJMoa1709030 KEYNOTE 054 – https://doi.org/10.1056/NEJMoa1802357EORTC18071 – https://doi.org/10.1016/S1470-2045(15)70122-1Mixture-Cure Modeling in CheckMate 238 – https://doi.org/10.1093/annonc/mdz255COMBI-AD – https://doi.org/10.1056/NEJMoa1708539Combi-Neo – https://doi.org/10.1016/S1470-2045(18)30015-9NeoCombi – https://doi.org/10.1016/S1470-2045(19)30331-6 OpACIN-neo – https://doi.org/10.1016/S1470-2045(19)30151-2

The therapeutic landscape in melanoma is evolving rapidly. In this podcast, Jonathan Lim (a member of the ESMO Young Oncologists Committee) interviews Dr Teresa Amaral (the current chair of the ESMO Young Oncologists Committee and an expert in melanoma) for an update on the current practice and advances in adjuvant and neoadjuvant therapies in melanoma. Dr Amaral summarises key practice-changing studies which have established the current recommendations in this field, including CheckMate 238, KEYNOTE 054, COMBI-AD, Combi-Neo, NeoCombi and opACIN-neo. We also deliberated on the toxicity profile of these therapies, and currently available evidence of neoadjuvant versus adjuvant therapies. Finally, we addressed how COVID-19 has affected the delivery of adjuvant and neoadjuvant therapies in patients with melanoma. Further reading: CheckMate 238 – <a href="https://doi.org/10.1056/NEJMoa1709030" rel="nofollow" target="_blank">https://doi.org/10.1056/NEJMoa1709030</a> KEYNOTE 054 – <a href="https://doi.org/10.1056/NEJMoa1802357" rel="nofollow" target="_blank">https://doi.org/10.1056/NEJMoa1802357</a> EORTC18071 – <a href="https://doi.org/10.1016/S1470-2045(15)70122-1" rel="nofollow" target="_blank">https://doi.org/10.1016/S1470-2045(15)70122-1</a> Mixture-Cure Modeling in CheckMate 238 – <a href="https://doi.org/10.1093/annonc/mdz255" rel="nofollow" target="_blank">https://doi.org/10.1093/annonc/mdz255</a> COMBI-AD – <a href="https://doi.org/10.1056/NEJMoa1708539" rel="nofollow" target="_blank">https://doi.org/10.1056/NEJMoa1708539</a> Combi-Neo – <a href="https://doi.org/10.1016/S1470-2045(18)30015-9" rel="nofollow" target="_blank">https://doi.org/10.1016/S1470-2045(18)30015-9</a> NeoCombi – <a href="https://doi.org/10.1016/S1470-2045(19)30331-6" rel="nofollow" target="_blank">https://doi.org/10.1016/S1470-2045(19)30331-6</a> OpACIN-neo – <a href="https://doi.org/10.1016/S1470-2045(19)30151-2" rel="nofollow" target="_blank">https://doi.org/10.1016/S1470-2045(19)30151-2</a>

Adjuvant and neoadjuvant therapies in melanoma

The advent of cancer immunotherapy has radically changed the field of oncology by improving the way many malignancies, including several aggressive and orphan diseases, are being treated with subsequent major improvement of patients’ prognosis. The first crucial and successful step in the field was the development of agents able to inactivate inhibitory immune receptors resulting in a subsequent increased anti-tumor response. Among them, antibodies blocking CTLA-4 (ipilimumab) and PD-1/PD-L1 (nivolumab, pembrolizumab, atezolizumab and durvalumab) are already widely available in clinical practice. More recently, to further improve the ability of the immune system to eradicate cancer cells, several other stimulatory or inhibitory molecules have been recognized as possible targets. ESMO Open has launched a special series of mini-reviews aiming to provide an update of the most interesting and upcoming targets in cancer immunotherapy including LAG3, TIM3, CD40, B7x, OX40, ICOS, VISTA, CD27, GITR and neoantigens. All these mini-reviews contain information on biological background (i.e. what the target is, where it is expressed and what is the physiological role as well as the expected effect when targeting it), drugs under development for targeting that specific molecule as well as current on-going clinical trials with targeted agents (including those in combination with other immune checkpoint inhibitors).In this podcast, Anna Berghof talks to Matteo Lambertini - Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.Read the Abstract: https://esmoopen.bmj.com/content/4/Suppl_3/e000795

The advent of cancer immunotherapy has radically changed the field of oncology by improving the way many malignancies, including several aggressive and orphan diseases, are being treated with subsequent major improvement of patients’ prognosis. The first crucial and successful step in the field was the development of agents able to inactivate inhibitory immune receptors resulting in a subsequent increased anti-tumor response. Among them, antibodies blocking CTLA-4 (ipilimumab) and PD-1/PD-L1 (nivolumab, pembrolizumab, atezolizumab and durvalumab) are already widely available in clinical practice. More recently, to further improve the ability of the immune system to eradicate cancer cells, several other stimulatory or inhibitory molecules have been recognized as possible targets. ESMO Open has launched a special series of mini-reviews aiming to provide an update of the most interesting and upcoming targets in cancer immunotherapy including LAG3, TIM3, CD40, B7x, OX40, ICOS, VISTA, CD27, GITR and neoantigens. All these mini-reviews contain information on biological background (i.e. what the target is, where it is expressed and what is the physiological role as well as the expected effect when targeting it), drugs under development for targeting that specific molecule as well as current on-going clinical trials with targeted agents (including those in combination with other immune checkpoint inhibitors). In this podcast, Anna Berghof talks to Matteo Lambertini - Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. Read the Abstract: <a href="https://esmoopen.bmj.com/content/4/Suppl_3/e000795" rel="nofollow" target="_blank">https://esmoopen.bmj.com/content/4/Suppl_3/e000795</a>

Emerging targets in cancer immunotherapy

Anna Berghof talks to Matteo Lambertini - Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.The year 2019 has brought relevant new biological and clinical evidence to further improve the care of breast cancer patients. Regarding biological knowledge, in addition to the many important steps forward in enhancing the understanding of several aspects related to tumor biology and treatment resistance, more predictive biomarkers have entered clinical use. In addition to knowing the status of hormone receptors and HER2, other biomarkers should now be tested in different disease subtypes and clinical situations including PD-L1, PIK3CA mutations and germline BRCA mutations.The clinical management of breast cancer patients has also significantly changed. Important evidence has become available to further personalize the choices of the best chemotherapy, endocrine treatment and targeted therapy approaches in both the advanced and early settings. Importantly, for patients with advanced breast cancer including those treated in the first-line setting, overall survival improvements have finally been observed in all disease subtypes thanks to the availability of more effective targeted agents. Many upcoming translational and clinical data are expected in 2020 with a great promise of further changing clinical practice in the breast cancer field. This is the case also for the triple-negative subtype where more effective and targeted treatment options beyond chemotherapy are expected to enter clinical use and improve patients’ outcomes and quality of life.Read the Abstract on the ESMO Open website: https://esmoopen.bmj.com/content/5/3/e000794

Anna Berghof talks to Matteo Lambertini - Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. The year 2019 has brought relevant new biological and clinical evidence to further improve the care of breast cancer patients. Regarding biological knowledge, in addition to the many important steps forward in enhancing the understanding of several aspects related to tumor biology and treatment resistance, more predictive biomarkers have entered clinical use. In addition to knowing the status of hormone receptors and HER2, other biomarkers should now be tested in different disease subtypes and clinical situations including PD-L1, PIK3CA mutations and germline BRCA mutations. The clinical management of breast cancer patients has also significantly changed. Important evidence has become available to further personalize the choices of the best chemotherapy, endocrine treatment and targeted therapy approaches in both the advanced and early settings. Importantly, for patients with advanced breast cancer including those treated in the first-line setting, overall survival improvements have finally been observed in all disease subtypes thanks to the availability of more effective targeted agents. Many upcoming translational and clinical data are expected in 2020 with a great promise of further changing clinical practice in the breast cancer field. This is the case also for the triple-negative subtype where more effective and targeted treatment options beyond chemotherapy are expected to enter clinical use and improve patients’ outcomes and quality of life. Read the Abstract on the ESMO Open website: <a href="https://esmoopen.bmj.com/content/5/3/e000794" rel="nofollow" target="_blank">https://esmoopen.bmj.com/content/5/3/e000794</a>

News in breast cancer 2019

The Covid-19 pandemic is currently active all over Europe and especially in Italy. In this podcast Anna Berghof discusses with Matteo Lambertini - Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy -  the difficulties of cancer treatment during this pandemic.Read the editorial: https://esmoopen.bmj.com/content/5/2/e000759

The Covid-19 pandemic is currently active all over Europe and especially in Italy. In this podcast Anna Berghof discusses with Matteo Lambertini - Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy - the difficulties of cancer treatment during this pandemic. Read the editorial: <a href="https://esmoopen.bmj.com/content/5/2/e000759" rel="nofollow" target="_blank">https://esmoopen.bmj.com/content/5/2/e000759</a>

Cancer care during the spread of Covid-19 in Italy: a young oncologist's perspective

Advanced cholangiocarcinoma is associated with a particular impaired survival prognosis. So far targeted therapies with relevant clinical efficacy are missing. isocitrate dehydrogenase 1 (IDH1) mutations are observed in a fraction of patients with cholangiocarcinoma. The ClarIDHy, a global, phase III, randomized, double-blind study of ivosidenib ersus placebo in patients with advanced cholangiocarcinoma with an IDH1 mutation met its primary endpoint. Therefore, ivosidenib is a promising new treatment opportunity in patients with Advanced cholangiocarcinoma harboring an IDH1 mutation.Read the Abstract: https://esmoopen.bmj.com/content/5/2/e000699

Advanced cholangiocarcinoma is associated with a particular impaired survival prognosis. So far targeted therapies with relevant clinical efficacy are missing. isocitrate dehydrogenase 1 (IDH1) mutations are observed in a fraction of patients with cholangiocarcinoma. The ClarIDHy, a global, phase III, randomized, double-blind study of ivosidenib ersus placebo in patients with advanced cholangiocarcinoma with an IDH1 mutation met its primary endpoint. Therefore, ivosidenib is a promising new treatment opportunity in patients with Advanced cholangiocarcinoma harboring an IDH1 mutation. Read the Abstract: <a href="https://esmoopen.bmj.com/content/5/2/e000699" rel="nofollow" target="_blank">https://esmoopen.bmj.com/content/5/2/e000699</a>

ESMO Presidential Symposium: ClarIDHy - ivosidenib in patients with advanced cholangiocarcinoma

Glioblastoma is the most frequent primary malignant brain tumor in adults. Methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) promotor is of prognostic as well as of predictive value, as patients with MGMT promotor methylation survive longer and have better responses to the alkylating chemotherapeutic agent temozolomid. The current first line therapy approaches after maximum safe resection include radio-chemotherapy with temozolomid, radio-chemotherapy with the combination of temozolomid and CCNU as well as tumor treating fields. Currently several early clinical studies investigate new treatment possibilists in glioblastoma.Listen to the podcast with Professor Ulrich Herrlinger, Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology, University Hospital Bonn, Germany.Read the Abstract: https://esmoopen.bmj.com/content/5/1/e000601

Glioblastoma is the most frequent primary malignant brain tumor in adults. Methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) promotor is of prognostic as well as of predictive value, as patients with MGMT promotor methylation survive longer and have better responses to the alkylating chemotherapeutic agent temozolomid. The current first line therapy approaches after maximum safe resection include radio-chemotherapy with temozolomid, radio-chemotherapy with the combination of temozolomid and CCNU as well as tumor treating fields. Currently several early clinical studies investigate new treatment possibilists in glioblastoma. Listen to the podcast with Professor Ulrich Herrlinger, Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology, University Hospital Bonn, Germany. Read the Abstract: <a href="https://esmoopen.bmj.com/content/5/1/e000601" rel="nofollow" target="_blank">https://esmoopen.bmj.com/content/5/1/e000601</a>

News on the horizon in glioblastoma therapy

There has been a lot of exciting trials in lung cancer reported in 2019. In this podcast, Jonathan Lim (YOC member) speaks to Professor Sanjay Popat about how these studies are practice-changing in the context of the current treatment landscape, and highlights what is on the horizon for 2020 (including targeting KRAS).Read the Abstract: https://esmoopen.bmj.com/content/5/1/e000676

There has been a lot of exciting trials in lung cancer reported in 2019. In this podcast, Jonathan Lim (YOC member) speaks to Professor Sanjay Popat about how these studies are practice-changing in the context of the current treatment landscape, and highlights what is on the horizon for 2020 (including targeting KRAS). Read the Abstract: <a href="https://esmoopen.bmj.com/content/5/1/e000676" rel="nofollow" target="_blank">https://esmoopen.bmj.com/content/5/1/e000676</a>

Highlights in Lung Cancer 2019

Immunotherapy approaches have revolutionized medical oncology in the last years. However, still only a fraction of patients is responding. Given the risk of side effects without efficacy, therefore, biomarkers providing reliable and reproducible prediction of response are urgently needed. In this podcast, next generation biomarkers including the challenge of branched genomic evolution of cancer are discussed by Professor Samra Turajlic, The Royal Marsden Hospital, London, UK.

Immunotherapy approaches have revolutionized medical oncology in the last years. However, still only a fraction of patients is responding. Given the risk of side effects without efficacy, therefore, biomarkers providing reliable and reproducible prediction of response are urgently needed. In this podcast, next generation biomarkers including the challenge of branched genomic evolution of cancer are discussed by Professor Samra Turajlic, The Royal Marsden Hospital, London, UK.

Current biomarkers in immunotherapy

ESMO Open is the European Society for Medical Oncology’s online-only, peer-reviewed Open Access journal, dedicated to publishing high-quality medical research and educational content from all disciplines of oncology, with a focus on innovative clinical and translational cancer research. The journal is published by BMJ on behalf of ESMO. http://esmoopen.bmj.com/* The purpose of this podcast is to educate and to inform. The content of this podcast does not constitute medical advice and it is not intended to function as a substitute for a healthcare practitioner’s judgement, patient care or treatment. The views expressed by contributors are those of the speakers. BMJ does not endorse any views or recommendations discussed or expressed on this podcast. Listeners should also be aware that professionals in the field may have different opinions. By listening to this podcast, listeners agree not to use its content as the basis for their own medical treatment or for the medical treatment of others.

ESMO Open is the European Society for Medical Oncology’s online-only, peer-reviewed Open Access journal, dedicated to publishing high-quality medical research and educational content from all disciplines of oncology, with a focus on innovative clinical and translational cancer research. The journal is published by BMJ on behalf of ESMO. <a href="http://esmoopen.bmj.com/" rel="nofollow" target="_blank">http://esmoopen.bmj.com/</a> * The purpose of this podcast is to educate and to inform. The content of this podcast does not constitute medical advice and it is not intended to function as a substitute for a healthcare practitioner’s judgement, patient care or treatment. The views expressed by contributors are those of the speakers. BMJ does not endorse any views or recommendations discussed or expressed on this podcast. Listeners should also be aware that professionals in the field may have different opinions. By listening to this podcast, listeners agree not to use its content as the basis for their own medical treatment or for the medical treatment of others.

ESMO Open

In this podcast, Marina Parry, ESMO Open Digital Editor, speaks to Elana Anastasio, Partnership Outreach Manager, and Brett Tomson, Scientific Outreach Manager, both from the Metastatic Breast Cancer (MBC) Project team at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, USA.The MBCproject is a novel model of a patient-partnered initiative whose aim is to accelerate the understanding of metastatic breast cancer by generating a massive open database of genomic information from patients’ tumour samples, alongside abstracted clinical information, and patient-reported data. In the podcast, we discuss the challenges faced by the team, the enthusiasm they were met with from patients, the logistical and operational hurdles they have overcome, the importance of finding a common language and building trust between participants and researchers, the role of social media and patient advocates, as well as the other patient-partnered projects this team has since initiated.The MBCproject organisers want to hear back from scientists and researchers about ideas or questions they have on how to use the existing data or new data you think would be good to try and generate. They encourage listeners to get in touch! Their website is https://www.mbcproject.org.

In this podcast, Marina Parry, ESMO Open Digital Editor, speaks to Elana Anastasio, Partnership Outreach Manager, and Brett Tomson, Scientific Outreach Manager, both from the Metastatic Breast Cancer (MBC) Project team at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, USA. The MBCproject is a novel model of a patient-partnered initiative whose aim is to accelerate the understanding of metastatic breast cancer by generating a massive open database of genomic information from patients’ tumour samples, alongside abstracted clinical information, and patient-reported data. In the podcast, we discuss the challenges faced by the team, the enthusiasm they were met with from patients, the logistical and operational hurdles they have overcome, the importance of finding a common language and building trust between participants and researchers, the role of social media and patient advocates, as well as the other patient-partnered projects this team has since initiated. The MBCproject organisers want to hear back from scientists and researchers about ideas or questions they have on how to use the existing data or new data you think would be good to try and generate. They encourage listeners to get in touch! Their website is <a href="https://www.mbcproject.org" rel="nofollow" target="_blank">https://www.mbcproject.org</a>.

The Metastatic Breast Cancer project: a novel patient-partnered initiative

The present podcast gives a short summary of the PAOLA-1 trial investigating the addition of Olaparib to bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer treated with platinum-based chemotherapy plus bevacizumab.Expert: Isabelle L. Ray-CoquardAffiliation: Centre Leon Bèrard, Université Claude Bernard Lyon, Groupe d'Investigateurs Nationaux pour l'Étude des Cancers de l'Ovaire (GINECO), Lyon, France

The present podcast gives a short summary of the PAOLA-1 trial investigating the addition of Olaparib to bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer treated with platinum-based chemotherapy plus bevacizumab. Expert: Isabelle L. Ray-Coquard Affiliation: Centre Leon Bèrard, Université Claude Bernard Lyon, Groupe d'Investigateurs Nationaux pour l'Étude des Cancers de l'Ovaire (GINECO), Lyon, France

ESMO Presidential Symposium: Phase III PAOLA-1: Olaparib in newly diagnosed, advanced ovarian cancer

Despite all the efforts done so far, access to essential drugs in Oncology is still asymmetric. In this podcast, Teresa Amaral, member of the ESMO YOC, interviews Professor Martine Piccart (Scientific Director of the Institut Jules Bordet, Universite Libre de Bruxelles, Belgium) that shares valuable insights on the work that has been done on this field by the ESMO Magnitude of Clinical Benefit Scale (ESMO – MCBS) group.You can find more information about the ESMO-MCBS group in the following publications:https://doi.org/10.1093/annonc/mdv249 http://dx.doi.org/10.1136/esmoopen-2017-000216More information on the ESMO Magnitude of Clinical Benefit Scale: Scale Evaluation Forms v1.0 &amp; v1.1 can be found here:https://www.esmo.org/Guidelines/ESMO-MCBS/Scale-Evaluation-Forms-v1.0-v1.1 You can read the complete Abstract relating to this podcast on the ESMO Open website: https://esmoopen.bmj.com/content/4/5/e000594.

Despite all the efforts done so far, access to essential drugs in Oncology is still asymmetric. In this podcast, Teresa Amaral, member of the ESMO YOC, interviews Professor Martine Piccart (Scientific Director of the Institut Jules Bordet, Universite Libre de Bruxelles, Belgium) that shares valuable insights on the work that has been done on this field by the ESMO Magnitude of Clinical Benefit Scale (ESMO – MCBS) group. You can find more information about the ESMO-MCBS group in the following publications: <a href="https://doi.org/10.1093/annonc/mdv249" rel="nofollow" target="_blank">https://doi.org/10.1093/annonc/mdv249</a> <a href="http://dx.doi.org/10.1136/esmoopen-2017-000216" rel="nofollow" target="_blank">http://dx.doi.org/10.1136/esmoopen-2017-000216</a> More information on the ESMO Magnitude of Clinical Benefit Scale: Scale Evaluation Forms v1.0 &amp; v1.1 can be found here: <a href="https://www.esmo.org/Guidelines/ESMO-MCBS/Scale-Evaluation-Forms-v1.0-v1.1" rel="nofollow" target="_blank">https://www.esmo.org/Guidelines/ESMO-MCBS/Scale-Evaluation-Forms-v1.0-v1.1</a> You can read the complete Abstract relating to this podcast on the ESMO Open website: <a href="https://esmoopen.bmj.com/content/4/5/e000594" rel="nofollow" target="_blank">https://esmoopen.bmj.com/content/4/5/e000594</a>.

The ESMO-Magnitude of Clinical Benefit Scale Group

The IMpassion130 trial was a global, randomized, double-blind, Phase III study of Atezolizumab + nab-paclitaxel vs. placebo + nab-paclitaxel in treatment naïve locally advanced or metastatic triple negative breast cancer patients. Here, progression free survival was statistically significantly longer in patients treated with the combination of Atezolizumab + nab-paclitaxel compared to placebo + nab-paclitaxel. The side effect profile was favorable as no unexpected toxicities were observed in the intervention compared to the control arm. In this podcast, Prof. Schmid provides insight on the response rate as well as the preliminary survival analysis of IMpassion130. Further possible biomarkers and the impact of the results on the treatment standard in breast cancer are discussed.Read the full Abstract on the ESMO Open website: https://esmoopen.bmj.com.

The IMpassion130 trial was a global, randomized, double-blind, Phase III study of Atezolizumab + nab-paclitaxel vs. placebo + nab-paclitaxel in treatment naïve locally advanced or metastatic triple negative breast cancer patients. Here, progression free survival was statistically significantly longer in patients treated with the combination of Atezolizumab + nab-paclitaxel compared to placebo + nab-paclitaxel. The side effect profile was favorable as no unexpected toxicities were observed in the intervention compared to the control arm. In this podcast, Prof. Schmid provides insight on the response rate as well as the preliminary survival analysis of IMpassion130. Further possible biomarkers and the impact of the results on the treatment standard in breast cancer are discussed. Read the full Abstract on the ESMO Open website: <a href="https://esmoopen.bmj.com" rel="nofollow" target="_blank">https://esmoopen.bmj.com</a>.

ESMO 2018 Presidential Symposium – IMpassion130: Atezolizumab in triple negative breast cancer

Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis.The phase III trial Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA) showed a significant increase in progression free survival. In the now available finale survival analysis also the overall survival showed a statistical significant increase.Expert: Suresh S. Ramalingam, Winship Cancer Institute of Emory University, Atlanta, GA

Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis. The phase III trial Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA) showed a significant increase in progression free survival. In the now available finale survival analysis also the overall survival showed a statistical significant increase. Expert: Suresh S. Ramalingam, Winship Cancer Institute of Emory University, Atlanta, GA

ESMO Presidential Symposium: Final overall survival analysis from the FLAURA trial

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 combination of chemotherapy with immune checkpoint inhibitor therapy according to the recently published data. Further, combination of immune checkpoint inhibitor-based therapy with chemotherapy and bevacizumab could be an option in patients with a driver mutation after the failure of available tyrosine kinase inhibitors.Listen to the podcast with Professor Johan Vansteenkiste, MD (Respiratory Oncology Unit and Trial Unit; Department of Respiratory DiseasesUniversity Hospitals KU Leuven; Catholic University Leuven, Belgium) and read the full Abstract on the ESMO Open website.

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 combination of chemotherapy with immune checkpoint inhibitor therapy according to the recently published data. Further, combination of immune checkpoint inhibitor-based therapy with chemotherapy and bevacizumab could be an option in patients with a driver mutation after the failure of available tyrosine kinase inhibitors. Listen to the podcast with Professor Johan Vansteenkiste, MD (Respiratory Oncology Unit and Trial Unit; Department of Respiratory Diseases University Hospitals KU Leuven; Catholic University Leuven, Belgium) and read the full Abstract on the ESMO Open website.

Immune checkpoint inhibitors for every non-small cell lung cancer patient

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 develop new compounds that either bind more effectively to known EGFR mutations, or which can bind to newly identified mutations.  The potential of both vertical and horizontal inhibition to achieve synergistic effects and so prolong tumor control was stressed.The highlights are presented by Josep Tabernero, of the Vall d'Hebron Institute of Oncology - Medical Oncology, Barcelona, Spain (jtabernero@vhio.net). This podcast is conducted by Anna Berghoff, Department of Medicine, Medical University of Vienna, Austria.

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 develop new compounds that either bind more effectively to known EGFR mutations, or which can bind to newly identified mutations. The potential of both vertical and horizontal inhibition to achieve synergistic effects and so prolong tumor control was stressed. The highlights are presented by Josep Tabernero, of the Vall d'Hebron Institute of Oncology - Medical Oncology, Barcelona, Spain (jtabernero@vhio.net). This podcast is conducted by Anna Berghoff, Department of Medicine, Medical University of Vienna, Austria.

Highlights from the ESMO Symposium on Signalling Pathways in Cancer 2016

In this podcast, Marina Parry, ESMO Open Digital Editor, speaks to Amanda Herbrand, Medical Oncologist Trainee working at University Hospital Basel, Switzerland, about her team’s work on off-label use (OLU) of Drug Treatments in Cancer Care, presented at ESMO Congress 2019 and a preprint of which is available on medRxiv: https://www.medrxiv.org/content/10.1101/19003152v1 With new drug treatments for cancer patients constantly being investigated in clinical trials, ensuring access to the ones which prove to be effective in improving patient care is critical. These drugs are initially assessed by medical authorities for their efficacy and cost effectiveness, which means it can take time before they are approved. However, physicians will sometimes wish to use therapies which have been shown to be effective in clinical trials but without specific approval in the disease setting they are treating. This leads to off-label use (OLU) of cancer therapies, which, depending on the healthcare system, is not covered by patients’ health insurance. Dr Herbrand and her team set out to understand what the reasons were behind insurers’ acceptance or denial of payment for OLU of drug treatments for cancer patients within the Swiss healthcare system. They investigated the relationship between reimbursement decisions and the underlying clinical evidence by extracting patient characteristics and treatment and reimbursement details of cancer drugs from over 3,000 patients in 3 Swiss hospitals, and created an evidence overview of the requested OLU indications. Their study provides a systematic assessment of OLU and its reimbursement reality in Switzerland. This may provide a better understanding of the access to cancer care that is regulated by health insurers and identify factors that determine the level of evidence-based cancer care in a highly diverse Western healthcare system. Further work will be undertaken as a follow up to this study.These data are preliminary and further work will be undertaken as a follow up to this study.

In this podcast, Marina Parry, ESMO Open Digital Editor, speaks to Amanda Herbrand, Medical Oncologist Trainee working at University Hospital Basel, Switzerland, about her team’s work on off-label use (OLU) of Drug Treatments in Cancer Care, presented at ESMO Congress 2019 and a preprint of which is available on medRxiv: <a href="https://www.medrxiv.org/content/10.1101/19003152v1" rel="nofollow" target="_blank">https://www.medrxiv.org/content/10.1101/19003152v1</a> With new drug treatments for cancer patients constantly being investigated in clinical trials, ensuring access to the ones which prove to be effective in improving patient care is critical. These drugs are initially assessed by medical authorities for their efficacy and cost effectiveness, which means it can take time before they are approved. However, physicians will sometimes wish to use therapies which have been shown to be effective in clinical trials but without specific approval in the disease setting they are treating. This leads to off-label use (OLU) of cancer therapies, which, depending on the healthcare system, is not covered by patients’ health insurance. Dr Herbrand and her team set out to understand what the reasons were behind insurers’ acceptance or denial of payment for OLU of drug treatments for cancer patients within the Swiss healthcare system. They investigated the relationship between reimbursement decisions and the underlying clinical evidence by extracting patient characteristics and treatment and reimbursement details of cancer drugs from over 3,000 patients in 3 Swiss hospitals, and created an evidence overview of the requested OLU indications. Their study provides a systematic assessment of OLU and its reimbursement reality in Switzerland. This may provide a better understanding of the access to cancer care that is regulated by health insurers and identify factors that determine the level of evidence-based cancer care in a highly diverse Western healthcare system. Further work will be undertaken as a follow up to this study. These data are preliminary and further work will be undertaken as a follow up to this study.

Reimbursement Reality for Off-label use (OLU) of Drug Treatments in Cancer Care

Biosimilars will soon become broadly available in the oncology field, raising important questions from both patients and healthcare providers. These questions need to be clarified upfront, in order to increase confidence in using these therapies. In this podcast, Teresa Amaral (YOC member) talks to Professor Josep Tabernero (ESMO President and Director of the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona about this timely topic – Biosimilars in Oncology.Read the full Abstract on the ESMO Open website: https://esmoopen.bmj.com/content/3/6/e000456

Biosimilars will soon become broadly available in the oncology field, raising important questions from both patients and healthcare providers. These questions need to be clarified upfront, in order to increase confidence in using these therapies. In this podcast, Teresa Amaral (YOC member) talks to Professor Josep Tabernero (ESMO President and Director of the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona about this timely topic – Biosimilars in Oncology. Read the full Abstract on the ESMO Open website: <a href="https://esmoopen.bmj.com/content/3/6/e000456" rel="nofollow" target="_blank">https://esmoopen.bmj.com/content/3/6/e000456</a>

Biosimilars in oncology

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 patient receiving now, in which dosage and how long has the autoimmune disease been stable. Patients that received a solid organ transplant pose an extra challenge. For patients that develop grade 4 autoimmune adverse events, re-treatment with immunotherapy should be extensively discussed. In case of severe autoimmune toxicity that does not respond to the treatments referred in the guidelines, and if the treating physician is not experienced with escalating immunosuppressive therapy, consultation with other centers with more familiarity and expertise on this topic should be considered.Read the abstract on the ESMO Open website: http://dx.doi.org/10.1136/esmoopen-2018-000395.

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 patient receiving now, in which dosage and how long has the autoimmune disease been stable. Patients that received a solid organ transplant pose an extra challenge. For patients that develop grade 4 autoimmune adverse events, re-treatment with immunotherapy should be extensively discussed. In case of severe autoimmune toxicity that does not respond to the treatments referred in the guidelines, and if the treating physician is not experienced with escalating immunosuppressive therapy, consultation with other centers with more familiarity and expertise on this topic should be considered. Read the abstract on the ESMO Open website: <a href="http://dx.doi.org/10.1136/esmoopen-2018-000395" rel="nofollow" target="_blank">http://dx.doi.org/10.1136/esmoopen-2018-000395</a>.

Questions asked in everyday practice: Immune Checkpoint Inhibitors

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 Pathology, Medical University of Vienna andLudwig Boltzmann Institute Applied Diagnostics) provides an overview of the current routinely used biomarkers as well as an outlook on what is on the horizon in epigenetic biomarkers.Read the Abstract on the ESMo Open website: https://esmoopen.bmj.com/content/3/5/e000416.

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 Pathology, Medical University of Vienna and Ludwig Boltzmann Institute Applied Diagnostics) provides an overview of the current routinely used biomarkers as well as an outlook on what is on the horizon in epigenetic biomarkers. Read the Abstract on the ESMo Open website: <a href="https://esmoopen.bmj.com/content/3/5/e000416" rel="nofollow" target="_blank">https://esmoopen.bmj.com/content/3/5/e000416</a>.

Epigenetic Biomarkers in Cancer

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