Esmo Open

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

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

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/NEJMoa1802357 EORTC18071 – https://doi.org/10.1016/S1470-2045(15)70122-1 Mixture-Cure Mode

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. A

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.

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

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

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

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

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.

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

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

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 p

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-2017-000216 More information on the ESMO Magnitude of Clinical Benefit Scale: Scale Evaluation Forms v1.0 & 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.

Professor Kim Margolin (Department of Medical Oncology, City of Hope National Medical Center, Duarte, California) discusses in this podcast the different treatment strategies as well as the clinical challenge of handling melanoma patients with brain metastases. Brain metastases are a particular problem of melanoma patients, as this complication occurs early and frequently. Further, brain metastases are associated with a high symptom burden. Recently, systemic treatment approaches including immunotherapy and tyrosine kinase inhibitors have become increasingly important in the management of melanoma brain metastases patients. Indeed, some patients with small, asymptomatic brain metastases without edema and need for steroid treatment might be candidates for a primarily systemic treatment. https://esmoopen.bmj.com/content/4/5/e000579

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.

Radiotherapy to the primary tumor has been a controversially discussed intervention in patients with newly diagnosed metastatic prostate cancer. Results of the STAMPEDE trial indicate that overall no survival advantage can be achieved by the addition of radiotherapy however subgroups might actually have a benefit. Here, patients with low volume, oligometastatic disease were shown to benefit in a predefined subgroup analysis. In this podcast, Dr. Parker provides insight on the practice changing impact of the STAMPE trial and gives an outlook what is next on the horizon in metastatic prostate cancer therapy. Read the full Abstract on the ESMO Open website: https://esmoopen.bmj.com/

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

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

In this podcast, Marina Parry, ESMO Open Digital Editor, speaks to Nicholas McGranahan, Junior Group Leader of the Cancer Genome Evolution Group at University College London’s Cancer Institute about the role of bioinformatics in translating genomics research into the clinic and his most recent paper “Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution”, Cell, 2017 https://www.cell.com/cell/pdf/S0092-8674(17)31185-6.pdf. Read the full Abstract on the ESMO Open website.