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 Modeling in CheckMate 238 – https://doi.org/10.1093/annonc/mdz255 COMBI-AD – https://doi.org/10.1056/NEJMoa1708539 Combi-Neo – https://doi.org/10.1016/S1470-2045(18)30015-9 NeoCombi – https://doi.org/10.1016/S1470-2045(19)30331-6 OpACIN-neo – https://doi.org/10.1016/S1470-2045(19)30151-2

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

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

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.