AACR 2017

Dr Bindra speaks with ecancer at AACR 2017 about the determination of PARP inhibitor sensitivity in brain tumour cells with IDH mutations He describes how, from screening of a CRISPR-Cas9 model of mutant IDH cells, synthetic lethality with PARP inhibitory therapy was uncovered. Dr Bindra highlights the current approval of PARP inhibitors in other indications, and outlines upcoming trials to further explore treatment options.

Prof Zakharia speaks with ecancer at AACR 2017 about adding indoximod, an IDO inhibitor, to pembrolizumab to treat advanced melanoma. In this interim report of results from 102 patients, he highlights that 52% of all patients respond, and that those figures increase when discounting patients with aggressive ocular melanoma. Compared to phase III single agent studies of pembrolizumab, these results are a marked improvement in response with minimal added toxicity, though Dr Zakharia cautions against direct comparison before further trials conclude.

Dr Lazar speaks with ecancer at AACR 2017 about what the WIN symposium offers, how it compares to other oncology meetings taking place around the globe, and what innovations he foresees in cancer treatment. He highlights the globally co-operative attitude of WIN consortium, reflected in the theme of this years conference, and introduces some key speakers. Dr Lazar notes room for improvement in streamlining early diagnosis and delivering the latest therapies to clinics globally, and considers the future indications of combination therapies.

Dr Topalian speaks with ecancer at AACR 2017 about the combination of ipilimumab and nivolumab for advanced melanoma. The results were presented at the conference by Dr James Larkin, and Dr Topalian comments on the response rates and overall survival in the combination. She considers the prospective value of BRAF and PD-1 biomarkers, and notes a significant increase in trial discontinuation due to adverse events.

Dr Silvia Marsoni presents trial data at AACR 2017 from the HERACLES trial, in which patient-derived xenografts were able to guide treatment choices for cetuximab-resistant colorectal cancer.

Dr Marsoni speaks with ecancer at AACR 2017 about the use of patient-derived xenografts of colorectal cancer to identify the role of HER2 amplification in cetuximab-resistant tumour types. She describes how a combination of lapatanib and trastuzumab can overcome this mutation, based on their success in treating HER2 breast cancer, and taking these results into treating patients can result in tumour shrinkage, and even complete responses.

Prof Schmid speaks with ecancer at AACR 2017 about the results from 150 triple negative breast cancer patients treated with atezolizumab. He highlights the best response to atezolizumab was among those receiving it as a first line therapy, and that the duration of response can reach up to 21 months. Median overall survival in the study remained at ~9 months, though responsive patients survival reached up to 2 years, which Prof Schmid describes as small subgroup. He goes on to describe his hopes for combination therapies which can deliver the same survival benefits to more patients.

Prof Stupp speaks with ecancer at AACR 2017 about developing treatments for glioblastoma, from temozolomide and chemotherapy to novel tumour treating fields. Prof Stupp describes how, by aligning polar molecules within cells using electromagnetic stimulation, it is possible to induce cell death within tumours, and summarises data from a randomised, multi-center phase III trial. He describes these results as a significant advance in treating historically aggressive and resilient brain cancers, and recommends it for use.

Prof Stupp presents data in a press conference at AACR 2017 of a phase III, multi-center randomised trial of using tumour-treating fields to augment chemotherapy in patients with aggressive brain tumours.

Dr Larkin presents results from Checkpoint 067, a trail of combined nivolumab and ipilimumab for advanced melanoma, at AACR 2017.

Dr Kaufman presents results at AACR 2017 of a trial administering avelumab to patients with advanced Merkel cell carcinoma who had not responded to chemotherapy.

Prof Brahmer presents data at AACR 2017 from a five year follow up of patients with non-small cell lung cancer treated with nivolumab.

Dr Hyman presents data from the SUMMIT trial at a press conference at AACR 2017, in which patients with solid tumours displaying mutations in HER2 or HER3 were treated with neratinib, and their response assessed. He describes positive responses in HER2 mutant breast cancer, cervical cancer and biliary cancer, though notes a lack of activity in bladder colorectal cancer and all solid tumours with HER3 mutations.

Prof Schmid presents research from a phase Ia expansion study at AACR 2017, evaluating responses to atezolizumab in patients with metastatic triple negative breast cancer.

Dr Robison speaks with ecancer at AACR 2017 about genomic factors behind the life-long risks to cancer survivors. From a patient cohort of over 4500 patients treated across 55 years, he describes how sequencing data from the first 3000 patients has revealed mutations in 156 predisposition genes linked to secondary lesions. Dr Robison notes the logistics required in tracking down former patients, and the limitations of data gathering when former patients have since died, possibly because of a second cancer.

Prof Brahmer speaks with ecancer at AACR 2017 about the long-term survivors of the CA209-003 study, who received nivolumab for advanced non-small cell lung cancer having at least one prior treatment. She compares the 5 year survival in this group against historic rates, 16% v 4%, and highlights PD-L1 staining as a means to highlight best-responders.

Dr Marrone speaks with ecancer at AACR 2017 about screening for prostate cancer in men, and the link to glycemic function. He describes an analysis of 5000 men from a large, long-term population study, which revealed associations between glycemic score on 3 biomarkers and risk of prostate. Dr Marrone summarises the significance of risks for differing biomarker groups, with some reaching clinical significance and a 3-fold increase of risk, and the overall importance of glycemic control.

Dr Mendelsohn speaks with ecancer at AACR 2017 about the aims of the WIN Consortium. He introduces the rationale of the annual conference, with key speakers on the latest in personalised therapy coming from around the world to discuss current practice and next steps. Dr Mendelsohn highlights the theme of this years conference as bringing the latest understandings of biomarkers and personalised care to clinical readiness, and encourages ongoing efforts in refining approaches and delivery of care. He highlights greater understanding of cell death pathways as offering novel opportunities in understanding diseases and therapies, and ongoing research into personalised therapy for varying populations.

Jessica Yasmine Islam speaks with ecancer at AACR 2017 about the changing burden of disease for HIV citizens who develop cancer. She notes the increased availability of life-extending anti-retroviral drugs, resulting in HIV patients living long enough to increase their risk of developing non-AIDS related cancers, and that by 2030 over 20% of HIV patients are projected to live over 65 years.

Dr Wargo speaks with ecancer at AACR 2017 about understanding the mechanisms of resistance in treating tumours, considering the influence of epigenetics, the tumour microenvironment and microbiota among others. The influence of the microbiome on cancer risk and treatment response was reviewed in an ecancer article last year, and she describes how research in mouse models translates to human trials. She considers faecal transplant, which is proving effective in managing C. diff infections, as a route for treating cancers in the near future. Dr Wargo goes on to discuss presentations from coworkers at the conference, including targeting stage III melanoma with BRAF inhibition before and after surgery.

Dr Rugo speaks with ecancer at AACR 2017 about the final analysis of MONARCH 1, a phase II trial of abemaciclib for advanced HR /HER2- breast cancer following chemotherapy. She summarises the cell cycle action of CDK4/6 inhibitors, noting cross-activity with oestrogen receptors, and the differing actions of related treatments ribociclib and palbociclib. Dr Rugo describes the treatment history of trial participants, and outlines the improvements in PFS with easily-managed adverse effects. She also notes effects of abemaciclib on kidney tububle function, which is "meaningless on a clinical basis".

Dr Das speaks with ecancer at AACR 2017 about the effect of tamoxifen before surgery on the genome of breast cancer cells. He reports that binding of oestrogen receptors deactivates p53, a tumour suppressor gene, based on sequencing after four weeks of tamoxifen therapy. Dr Das describes these findings pointing towards p53 activation as a predictor of tamoxifen response, with further trials to confirm utility in stratifying patients with triple negative breast cancer.

Dr Farago speaks with ecancer at AACR 2017 about results from a phase I/II study of treating patients with small cell lung cancer (SCLC) following relapsed after chemotherapy. She describes the rationale of adding olaparib, a PARP inhibitor preventing DNA repair, to temozolomide which induces single strand breaks, with a hopeful synergy for controllable cell death within tumours. Dr Farago describes the doses in the trial as well tolerated, with a response rate of 48% and a median PFS of 5.6 months. She also highlights the utility of patient derived xenografts to chart patient responses through time, and identify stages of resistance and response.

Dr Hyman speaks with ecancer at AACR 2017 to discuss results of the phase II SUMMIT trial of neratinib, which you can read more about here, or watch the press conference in which these results were presented. He describes the response of patients with HER2 mutations to neratinib, most notably in breast, cervical and biliary cancers, and considers the influence of tumour type and specific mutation to explain the lack of responses in patients with HER3 mutations and HER2 colorectal tumours.

Dr Kaufman speaks with ecancer at AACR 2017 about the effectiveness of anti-PD-L1 avelumab in treating Merkel cell carcinoma (MCC) in patients who had been previously treated with chemotherapy. He describes results from 88 patients with metastatic disease, who at 6 months follow-up had 31% response, and 33% response at 1 year. Dr Kaufman notes the recent FDA approval of avelumab in this setting, and considers other possible applications.