ESMO 2016

Prof Bertrand Tombal (Saint-Luc Hospital, Brussels, Belgium) and Dr Mark Beresford (Royal United Hospitals Bath, Bath, UK) have a focused discussion looking at overall safety of treatment and current predictive markers within prostate cancer at ESMO 2016. The experts initially discuss the results from the long-term safety study in patients treated with abiraterone acetate plus prednisone for greater than or equal to 4 years. The results confirmed that no new safety signals were associated with prolonged treatment with abiraterone acetate plus prednisone in castration-resistant prostate cancer. Additional discussions on patient safety then looked at the question around fatigue in patients with castration-resistance whilst receiving enzalutimide treatment. The results from this study showed slightly higher levels of fatigue in patients receiving enzalutimide compared with the control arm. It was remarked that this study did not take other factors into account such as cognitive effects of treatment which would be considered within the routine clinical setting. Although overall the results from this study were reassuring. The post hoc analysis of the ICELAND study were discussed and highlight that patients receiving CAD, CSS and time to PSA (CRPC) progression do not differ according to testosterone levels in the first year of therapy, which may be due to effectiveness of leuprorelin. Finally, both discussants shared their views on whether NLR is a helpful prognostic indicator of the inflammatory condition in patients and whether there is a predictive correlation with prognosis.

ecancer Editor in Chief, Prof Gordon McVie provides us with a roundup of all the ESMO 2016 highlights. Prof McVie discusses the following: Prof Alexander Eggermont - ipilimumab for melanoma Dr Arjun Balar - pembrolizumab for urothelial cancer Dr Gabriel Hortobagyi - ribociclib for breast cancer Dr Fabrice Barlesi - atezolizumab for lung cancer Dr Martin Reck - pembrolizumab vs chemo for NSCLC Dr Corey Langer - pembrolizumab plus chemo for NSCLC Dr Giorgio Scagliotti - ceritinib for ALK NSCLC Dr Tony Choeuiri - cabozantinib for kidney cancer Dr Mansoor Raza Mirza - niraparib for ovarian cancer

In this roundtable discussion, chaired by Dr Eleni Efstathiou (MD Anderson Cancer Center, Houston, USA) for ecancertv, experts Prof Karim Fizazi (Cancer Medicine at the Institut Gustave Roussy, Villejuif, France), and Dr Chris Parker (The Royal Marsden, London, UK) highlight and debate advances in prostate cancer from the ESMO 2016 conference. Our clinical experts share their thoughts on some of the clinical practice changing data overall from ESMO 2016 and debate the more controversial aspects of the ESMO prostate cancer data. One of the most widely discussed conversations at the congress was how to treat patents with low volume disease. The subgroup analysis of the CHAARTED data indicate that there was no overall survival data for this group of patients. However the panel discuss the bigger picture and how the meta-analysis data may potentially differ and indicate a different clinical treatment strategy. The panel also discuss whether PTEN loss is a predictive biomarker with the AKT inhibitor ipatsertib when combined with abiraterone acetate. The study indicates that PTEN loss looks like a promising predictive biomarker for mCRPC and warrants further development of Ipat to select patients with PTEN loss and improve clinical outcomes. Other highlights include the AFFINITY results, KEYNOTE-028 data and the future of BRCA testing for prostate cancer patients.

Dr Choueiri presents, at a press conference at ESMO 2016, results of the CABOSUN comparitive trial, which assessed outcomes of patients with metastatic rencal cell carcinoma receiving cabozantinib versus sunitnib. Both drugs are tyrosine kinase inhibitors (TKIs) targeting VEGFR, however cabozantinib has additional actions in inhibition of MET and AXL. He describes the results, which demonstrate improved progression free survival in the cabozantinib arm, and considers its progression towards wider adoption and approval.

Dr Bang speaks with ecancer at ESMO 2016 to discuss outcomes of the GOLD trial, combining olaparib and paclitaxel to treat advanced gastric cancer. Compared to paclitaxel alone, olaparib extended overall survival and progression free survival, but did not reach a p value indicating statistical significance. While the trial is negative, Dr Bang describes the outcomes of indicative of a role for olaparib in future studies.

Dr Ravaud presents, at a press conference at ESMO 2016, results from a one-year trial of sunitinib vs placebo for post-nephrectomy high-risk renal cancer patients. This phase III trial found a longer disease-free survival in the sunitinib arm, and Dr Ravaud describes this extension with the manageable toxicity profile as recommending factors for sunitinib in adjuvant therapy.

Dr Gronchi presents, at a press conference at ESMO 2016, results from a trial assessing response of patients with advanced soft tissue sarcoma to adjuvant epirubicin plus ifosfamide compared to those receiving a tailored chemo regimen based on histology subgrouping He reports significantly improved relapse-free survival and overall survival for patients receiving adjuvant chemo, thought notes the trial is a technical failure due to being powered for the histology-tailored sub types which did not show any benefit.

Dr Fizazi presents, at a press conference at ESMO 2016, the results of the AFFINITY trial of custirsen, a clusterin upstream inhibitor which had previous indications of improved clinical outcomes for castration resistant prostate cancer. He describes the results from the AFFINITY trial as failing to reach significant difference in overall survival, and considers future paths for clusterin-targeted cancer therapy.

Dr Pandha speaks with ecancertv at ESMO 2016 about two trials of coxsackie virus as an immune modulator. Dr Pandha describes results from the CANON trial of virotherapy for bladder cancer, and the STORM / KEYNOTE200 trial which combined virotherapy with immune modulator pembrolizumab. He describes how viral stimulation of immune activity, further enhanced by checkpoint inhibitors, can have significant outcomes, and considers wider adoption of virotherapy to complement other treatment modalities.

Dr Cohen speaks with ecancertv at ESMO 2016 about the Activ8 trial, which sought to combine cetuximab and chemotherapy with toll-like-receptor agonist motolimod. He describes the pathways by which motolimod redirects CD8 T cells towards non-immunogenic tumours, though reports the Activ8 trial as a statistically negative trial having not met its end-points. Thought a negative trial in this instance, he describes the immune activity in a subset of patients who responded best as indicative of motolimods potential for future trials.

Prof Brünner talks to ecancertv at ESMO 2016 about his institute's work looking at new pathways in colorectal cancer. Biomarkers and screening are a focus, as well as combating drug resistance and drug repurposing.

Prof Fizazi meets with ecancertv at ESMO 2016 to discuss the results of the AFFINITY trial of custirsen, a clusterin upstream inhibitor which had previous indications of improved clinical outcomes for castration resistant prostate cancer. He describes the results from the AFFINITY trial as failing to reach significant difference in overall survival, and considers future paths for clusterin-targeted cancer therapy.

Dr Hamid speaks with ecancertv at ESMO 2016 about the outcomes of a phase I study into the responses to combined PD-1 and PD-L1 inhibition in multiple tumour sites. PD-1 and PD-L1 have been targets of immune checkpoint inhibitor therapy independently across multiple cancer types and sites, and Dr Hamid describes the initial results of co-targeting both at once. He introduces upcoming phase II trials in bladder cancer, and considers how to improve patient responses for those expressing either high or low levels of the biomarkers.

Prof Van Cutsem meets with ecancertv at ESMO 2016 to discuss the different treatment profiles of left or right sided colon cancers, as determined through the CRYSTAL study. He describes how, depending on the tumour locations in reference to the splenic fracture, left sided tumours responded more to the cetuximab FOLFIRI being administered in the trial, and considers how sidedness as a substitute for biomarkers is only a starting point for prognosis. Dr Van Cutsem reflects on other presentations from the conference, how they will guide clinical development and may result in improvements of care.

ecancer blogger Dr Gyawali gives his scientific highlights from ESMO 2016, covering the likely impact of the research.

Prof Van Cutsem speaks with ecancertv at ESMO 2016 about the LUME trial assessing response of patients with colon cancer to nintedanib. He describes the study design, including the multiple targets of nintedanib, and the mixed outcomes of improves PFS but no overall survival benefit.

Dr Gronchi speaks with ecancertv at ESMO 2016 about the responses of patients with advanced soft tissue sarcoma to adjuvant epirubicin plus ifosfamide compared to those receiving a tailored chemo regimen based on histology subgrouping He reports significantly improved relapse-free survival and overall survival for patients receiving adjuvant chemo, thought notes the trial is a technical failure due to being powered for the histology-tailored sub types which did not show any benefit.

Dr Cervantes, Scientific Chair of ESMO 2016, summarises the breaking research presented, and gives his highlights of the conference. He discusses the trials of immune checkpoint modulators in multiple tumour sites, especially the data on lung cancer presented in Sundays press conference, and the progression of some therapies to first-line indications. Dr Cervantes also considers novel combinations of molecules and modalities, many of which synergise with or magnify the impact of immunotherapy, and reflects on cell cycle modulation through CDK pathways as opening outcomes for women with metastatic breast cancer. Overall, Dr Cervantes describes the research from this years conference as changing the way cancer therapy develops for clinicians, and most importantly for patients.

Dr Gyawali meets with ecancertv at ESMO 2016 to discuss the safety profile of sorafenib, with a 27% increase in the risk of grade 4 and 5 adverse events compared to standard care. He describes the context of the results from this meta-analysis, considering the balancing of risk and outcome for patients, and the impact of treatment-related hospitalisation on quality of life.

Dr Ravaud speaks with ecancertv at ESMO 2016 about results from a one-year trial of sunitinib vs placebo for post-nephrectomy high-risk renal cancer patients. This phase III trial found a longer disease-free survival in the sunitinib arm, and Dr Ravaud describes this extension with the manageable toxicity profile as recommending factors for sunitinib in adjuvant therapy.

Dr Arafat speaks with ecancertv at ESMO 2016 about TRAIL, an apoptotic receptor - ligand pairing with modulated expression in cancer cells, which he believes could restore cell death to tumours. He considers delivery systems by which TRAIL might be introduced, and its synergistic potential with chemotherapy or radiotherapy.

Dr Chowdhury talks to ecancertv at ESMO 2016 about the Cancer Registry, that monitors the treatments and outcomes of over 3,000 patients across Europe with metastatic castration-resistant prostate cancer (mCRPC).

Dr Stefan Zimmerman speaks with ecancertv at ESMO 2016 to summarise newly reported advances in lung cancer. He comments on the press conference presentations of Dr Giorgio Scagliotti, Dr Martin Reck, Dr Fabrice Barlesi and Dr Corey Langer who spoke about different immunologic and cell cycle therapies improving progression free survival and overall survival of patients.

Prof Tang speaks with ecancertv at ESMO 2016 about successes with ANG1005, a conjugate of paclitaxel with a peptide which can cross the blood brain barrier. He describes the mechanism of the molecules infiltration and action within brain metastases of breast cancer, and considers further avenues for development through modified conjugates, and treatment of primary brain lesions.

Dr Scagliotti presents, at a press conference at ESMO 2016, results from the ASCEND-5 trial of ceritinib, a kinase inhibitor targeting ALK rearrangements, for patients with advanced non-small cell lung cancer who had relapsed following crizotinib therapy.

Dr Barlesi presents, at a press conference at ESMO 2016, results from the OAK study, which found atezolizumab improved median overall survival for patients with advanced non-small cell lung cancer, especially those stratified by high PD-1 expression.

Dr Pantziarka speaks with ecancertv at ESMO 2016 about current efforts, and regulatory hurdles, towards the repurposing of medicines that are approved to treat other diseases, but have the potential to improve cancer patient outcomes. He discusses how propranolol, a beta-blocker commonly prescribed to treat hypertension, might be a cheap and effective adjuvant in cancer therapy. Dr Pantziarka is also joined by Dr Lydie Meheus of The Anticancer Fund, Belgium.

Dr Reck presents, at a press conference at ESMO 2016, results from the KEYNOTE-024 trial which he believes recommend the use of PD1 antibody pembrolizumab as first-line therapy for patients with NSCLC whose tumours express high levels of PDL-1. These results complement those presented by Dr Langer, who reports improved outcomes for NSCLC patients receiving firstline pembrolizumab and chemotherapy.

Dr Corey Langer presents, at press conference at ESMO 2016, results from the KEYNOTE-021 trial. The trial found that the addition of pembrolizumab, a PD-1 antibody, to standard first-line chemotherapy for treatment-naive advanced NSCLC achieved significantly longer progression free survival, a great objective response rate, and a well tolerated toxicity profile. These results complement those presented by Dr Martin Reck, who presented results from KEYNOTE-024 which recommend pembrolizumab as a firstline therapy for NSCLC patients with high levels of PDL-1 expression.

Dr Riechelmann speaks with ecancertv at ESMO 2016 about carcinoid syndrome, which results from carcinoid tumour invasion of organ sites and stimulation of the release of hormones. She describes the symptoms and impacts of carcinoid syndrome on patients quality of life, and introduces her review of current literature into understanding of the disease. Dr Riechelmann calls for studies into the mechanistic action and incidence of carcinoid syndrome, rather than relying on retrospective analyses.

Dr Balmaña speaks with ecancer at ESMO 2016 about using lurbinectedin, a trabectidin analogue, in the treatment of breast cancer. She describes its mechanism of action, aiming to use the resulting gene suppression and DNA damage selectively in tumour cells, and gives results of progression-free and overall survival among multiple patient cohorts. Dr Balmaña outlines further research into the timing and exposure factors that may influence patient response to lurbinectedin, especially PARP inhibitors, and studies of its activity in other tumour sites.

Dr Gnant speaks with ecancertv at ESMO 2016, reviewing the conference controversy session: Should combined endocrine therapy with targeted agents now be the standard of care for ER metastatic breast cancer? Weighing cost and safety profile, Dr Gnant thinks further specificity in patient subtypes may streamline treatment selection.

Dr Rodón talks to ecancertv at ESMO 2016 about the innovative uses of a new kinase inhibitor for angiogenesis and fibroblast growth factor receptors. He also discusses how some tumours with genetic alterations could benefit from the use of this new class of drug.

Dr Doherty talks to ecancertv at ESMO 2016 about the experience of lung cancer patients and their caregivers, based on a survey by Lung Cancer Canada. Doherty focussed on the responses from caregivers. Mood changes, fatigue, and loss of weight were sited as key problems, as well as the negative stigma attached to the diagnosis due to its association with smoking.

Dr Seoane talks to ecancertv at ESMO 2016 about modelling cell lines and determining biomarkers for better prognosis. Considering the pathways through which cancers develop insenstivity to different therapies, Dr Seoane highlights the need for greater understanding and proactive prevention of resistance with novel treatments and combination therapy.

Dr Gnant talks to ecancertv at ESMO 2016 about the results of the MONALEESA-2 and PALOMA-2 trials, which confirm, he says, that the addition of cell cycle inhibitors (specifically, CDK4/6) can be of great benefit to patients with metastatic breast cancer. He discusses the results of both trials with particular regards to toxicity.

Dr Banerjee speaks with ecancertv at ESMO 2016 about the primary results from the CORAL trial. She outlines the background of anti-androgen therapy which has led to abiraterone, a CIP17 upstream inhibitor of androgen and oestrogen, and considers other avenues of research that may help patients with advanced ovarian cancer. Dr Banerjee explains that, while 26% of patients in the trial had a clinical benefit and 14% a prolonged benefit, only 1 patient of the cohort of 42 was fully responsive, leading to cessation of the study. With these results in mind, she believes that further understanding of highly responsive patient subtypes will help in advancing ovarian cancer care for all patients.

Dr Cruz speaks with ecancer at ESMO 2016 about trials for lurbinectedin in patients for whom PARP inhibition is no longer and option. She describes the mechanisms by which resistance to other medications can be subverted by lurbinectedin, and reports its suitability even for tumours with resistance to standard therapy cisplatin.

Dr Barlesi speaks with ecancertv at ESMO 2016 about results from the OAK study, in which 1225 non-small cell lung cancer patients who had previously received treatment were stratified based on PD-L1 status and treatment history, then received either PD-1 inhibitor atezolizumab or standard therapy docetaxel. He describes the improvements in patients median survival across both groups, though reports a 56% greater response for patients with the highest levels of PD-L1 expression, and considers the treatment duration and associated toxicities of both arms in the trial.

Dr Gyawali meets with ecancertv at ESMO 2016 to discuss the value of negative trials, considering the slow progression in treating ovarian cancer. He considers statistically positive studies that have limited benefit for patient survivals, trials finding improved progression-free survival but which fail for not meeting other primary endpoints, and the central importance of patient benefit in trial design.

Dr Walker speaks with ecancertv at ESMO 2016 about the analytical consistency of four PDL-1 assays. She describes results based on assaying samples from head and neck cancers, with three of four assays being tested reaching a high degree of result harmonisation.

Dr Langer speaks with ecancertv at ESMO 2016 about the results from the KEYNOTE-021 trial. The trial found that the addition of pembrolizumab, a PD-1 antibody, to standard first-line chemotherapy for treatment-naive advanced NSCLC achieved significantly longer progression free survival, a great objective response rate, and a well-tolerated toxicity profile.