Oncology Times - Ot Broadcasts From The Ipad Archives

A clinically meaningful benefit in overall survival was found in the second interim analysis of the randomized, double-blind, Phase III KEYNOTE-A18 study of immunotherapy together with concurrent chemoradiotherapy among 1,060 patients who had newly diagnosed, previously untreated high-risk locally advanced cervical cancer. A multinational team of researchers, led from Italy, reported findings at the ESMO Congress 2024. There was a statistically significant increase in 36-month overall survival in patients treated with pembrolizumab, in addition to chemoradiotherapy, in comparison to those in the control group who received standard chemoradiation alone.

In this podcast episode, Ruchika Talwar, MD, sits down with Rick Baehner, MD, Chief Medical Officer of Precision Oncology at Exact Sciences and Clinical Professor of Pathology at University of California, San Francisco, to discuss the importance of ultra-comprehensive genomic profiling in advanced cancer therapy selection. The two talk about the OncoExTra® test from Exact Sciences, which includes whole-exome DNA sequencing and whole-transcriptome RNA sequencing, and how the latest updates to industry guidelines will continue to influence approaches to cancer care.

The prospect of markedly raising chemotherapy response rates and extending patient survival has been held out by scientists reporting a new AI-powered digital tool to optimize cancer management for individual patients.   The tool creates a “digital twin” for each patient that makes it possible to predict response to specific treatment regimens and confidently predict outcomes, according to findings from a study reported by scientists at the EORTC-NCI-AACR 2024 Molecular Targets and Cancer Therapeutics Symposium.

The prospect of a minimally toxic, chemotherapy-free cure for hepatoblastoma is held out by findings from a mouse model using the small-molecule drug WNTinib that inhibits the Wnt signaling pathway involved with cancer growth.   Lead author Ugnė Balaševičiūtė, a pre-doctoral researcher in Translational Research of the Hepatic Oncology Group led by Josep M. Llovet, Professor at the Institut D'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) in Barcelona, Spain, reported that the CTNNB1 (catenin beta-1 protein) gene targeted by WNTinib was expressed in 90 percent of all hepatoblastomas. Hopes were high that a safer alternative to chemotherapy in humans was on the way.

A chemotherapy-free combination of two anti-human epidermal growth factor receptor 2 (anti-HER2) agents brought clinically meaningful responses to patients with bile duct cancers testing positive for HER2 or with mutated HER2 in research from Japan reported at the EORTC-NCI-AACR 2024 Molecular Targets and Cancer Therapeutics Symposium held in Barcelona, Spain.   In the SGNTUC-019 Phase II basket study of 217 patients, who had a variety of previously treated solid tumors with HER2 overexpressed, amplified, or mutated, a combination of tucatinib with trastuzumab brought significant clinical responses among those with biliary tract tumors in addition to those with breast cancer.

The fibroblast growth factor receptor-3 (FGFR-3) inhibitor TYRA-300 has been found safe with dose-dependent responses and disease control in the Phase I SURF301 trial. The study included 41 patients who had been heavily pre-treated for their advanced solid tumors with activating FGFR3 mutations/fusions, bringing the hope of avoiding toxicities from the use of non-specific pan-FGFR inhibition.   The findings were reported by Ben Tran, MBBS, FRACP, at the 2024 EORTC-NCI-AACR 2024 Molecular Targets and Cancer Therapeutics Symposium held in Barcelona, Spain. Tran is a Medical Oncologist and Associate Professor at the Peter MacCallum Cancer Centre Melbourne, Australia. He also is Chair of the Germ Cell Tumour Subcommittee for the Australian and New Zealand Urological and Prostate Cancer Trials.

The mini-protein radiopharmaceutical AKY-1189, designed to deliver the alpha-emitting isotope Actinium-225 (225Ac) to tumors expressing the Nectin-4 transmembrane protein, has been found to achieve favorable dosing to tumors, while minimizing exposure to non-target tissues, including the kidney. Data on the biodistribution and tumor uptake of the drug were reported at the 2024 EORTC-NCI-AACR 2024 Molecular Targets and Cancer Therapeutics Symposium held in Barcelona. Researcher Machaba Mike Sathekge, PhD, Professor and Head of the Department of Nuclear Medicine at the University of Pretoria and Steve Biko Academic Hospital in South Africa. He is also CEO of Nuclear Medicine Research Infrastructure and Chairman of the South African Medical Research Council.

In a Phase I study with 318 patients in China and Australia the antibody-drug conjugate (ADC) IBI354 was found to be safe and have promising efficacy in patients whose breast and other solid tumors tested positive for HER2 or were categorized as “HER2-low.” At ESMO Congress 2024, the study also reported a low rate of interstitial lung disease in patients treated with the ADC. Oncology Times correspondent Peter Goodwin talked with Christina Teng, PhD, the presenting author of the new research from Scientia Clinical Research and the Prince of Wales Hospital in Sydney, Australia.

Sustained responses and long-term overall survival have resulted from checkpoint inhibitor therapy for advanced melanoma, transforming the prognosis for as many as half of patients. This is according to 10-year survival outcomes from the Phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma that were reported at the ESMO Congress 2024.   At the conference, Oncology Times reporter, Peter Goodwin, caught up with James Larkin, FRCP, PhD, Professor and Medical Oncologist at the Royal Marsden Hospital in London.

The addition of preoperative chemoradiation therapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone in patients with resectable gastric or gastroesophageal junction adenocarcinomas. The multi-continent, Phase III randomized TOPGEAR trial has definitively found no benefit from adding radiation before surgery in terms of overall or progression-free survival. This clear finding was reported simultaneously in the New England Journal of Medicine and at the ESMO 2024 Congress held in Barcelona, Spain. After presenting the findings , first author Trevor Leong, MD, Radiation Oncologist at the Peter McCallum Cancer Centre in Melbourne, Australia, met up with Oncology Times reporter Peter Goodwin.

Patients with muscle-invasive bladder cancer experienced “clinically meaningful” improvements in key outcomes—event-free survival and overall survival—when the immune checkpoint inhibitor durvalumab was added to their standard neoadjuvant chemotherapy. This was in research findings, reported at the ESMO Congress 2024, from the NIAGARA randomized Phase Ill trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in patients with cisplatin-eligible muscle-invasive bladder cancer. After his talk at the ESMO Barcelona conference, first author Thomas Powles, MBBS, MRCP, MD, from the Barts Cancer Institute at Queen Mary University of London, UK, met up with Oncology Times correspondent Peter Goodwin.

When patients with recurrent high-grade glioblastoma were treated with autologous myeloid dendritic cells, they had clinical responses described as “encouraging” in a Phase I clinical trial reported at the ESMO Congress 2024. Cells harvested from each patient were injected directly into the resection cavity brain tissue lining after surgery. Patients also received intracranial injections of the checkpoint inhibitor combination: nivolumab + ipilimumab. At the conference, Oncology Times reporter Peter Goodwin caught up with lead author of the study, Bart Neyns, MD, PhD, Head of Medical Oncology at the Vrije Universiteit Brussel in the University Hospital Brussels Faculty of Medicine & Pharmacy in Belgium.

Patients with newly diagnosed, surgically resected MGMT-unmethylated glioblastoma may benefit from treatment with a therapeutic mRNA vaccine called CVGBM, according to findings from a first-in-human, Phase I safety and dose-escalation study from Tübingen, Germany, reported at the ESMO Congress 2024 held in Barcelona. The CVGBM vaccine encodes multiple molecular features derived from tumor-associated antigens, all of which were judged to be potentially relevant in glioblastoma. After reporting her group’s findings to the ESMO Barcelona meeting, first author Ghazaleh Tabatabai, MD, PhD, a neurologist, Professor of Neuro-Oncology, and Chair of the Department of Neurology and Interdisciplinary Neuro-Oncology at the University Hospital, Tübingen, Germany, talked about the findings with Oncology Times reporter Peter Goodwin.

A large, expanded-cohort pooled analysis of neoadjuvant immunotherapy for patients with resectable Stage III melanoma has reported very high rates of durable survival. The findings from the world’s biggest center of expertise in melanoma were announced at ESMO Congress 2024.   The study included patients from clinical trials and real-world studies who had pure immune checkpoint inhibitor neoadjuvant therapy, or combinations including BRAF/MEK targeted therapy. After giving her talk in Barcelona, lead investigator Georgina Long, AO, PhD, MBBS, FRACP, Professor and Co-Medical Director at the Melanoma Institute Australia, University of Sydney, gave Oncology Times reporter Peter Goodwin the details.

Drug resistance can be delayed and treatment outcomes predicted in patients with ovarian cancer with the help of relatively low-cost molecular precision management techniques using liquid biopsies. These are being developed by a team at the University of California in Los Angeles (UCLA) led by Jian Yu Rao, MD, Vice Chair of Diagnostic Technology Innovation at UCLA, where he is also Chief of Cytopathology and Director of International Telepathology.   At the 2024 Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) held in Xiamen, China, Rao gave Oncology Times reporter Peter Goodwin details of the molecular methods he had just outlined to the conference.

Important findings about the benefit of neoadjuvant therapies, especially those involving checkpoint inhibition, have been reported at the ESMO 2024 Congress. Rebecca Dent, MD, Scientific Chair of the meeting, as well as Medical Oncologist and Deputy Chief Executive Officer at the National Cancer Center in Singapore (with a special interest in all aspects of triple-negative breast cancer), shared the key areas of progress covered by the meeting.

The escalating danger of cardiac toxicity posed by a range of increasingly effective anti-cancer therapies is insufficiently understood, according to the head of a world center of excellence for the study of cardio-oncology in northern China.    At a special session devoted to cardio-oncology held at the Chinese Society of Clinical Oncology (CSCO) 2024 Annual Meeting, the challenges of cardio-oncology were examined by a committee of experts with reference to the CSCO Clinical Practice Guide for Tumor Cardiology.   Among the speakers was cardiologist Yun-Long Xia, MD, PhD, FESC, FHRS, Head of Cardiovascular Medicine at Dalian Medical University in China. Afterward, he talked about their conclusions with Oncology Times reporter Peter Goodwin.

Details of the expanding range of cell therapies beyond hematologic malignancy were reported at the 2024 Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) by Oliver Dorigo, MD, PhD, Director of the Division of Gynecologic Oncology at the Stanford Women's Cancer Center in Stanford University. After his talk at CSCO, Dorigo told Oncology Times reporter Peter Goodwin about the promise cell therapies held for improving outcomes in ovarian cancer and other solid tumors, as well as the benefit of the exchange of ideas flowing between China, U.S., and other global players in this young science.

An assessment of progress with antibody-drug conjugates (ADCs) for the treatment of HER2-dependent metastatic breast cancer was given at the 2024 Chinese Society of Clinical Oncology (CSCO) Annual Meeting. The President-Elect of the European Society for Medical Oncology (ESMO), Giuseppe Curigliano, MD, PhD, Director of the Early Drug Development for Innovative Therapies Division at the European Institute of Oncology and the University of Milano in Italy, told Oncology Times reporter Peter Goodwin about the broadening scope of ADCs in breast cancer and his reasons for encouraging ESMO and CSCO to continue to expand their co-operation.

At the opening session of the Chinese Society of Clinical Oncology (CSCO) 2024 Annual Meeting, attended by nearly 30,000 cancer specialists, Oncology Times reporter Peter Goodwin asked the President of CSCO, Xu Ruihua, MD, PhD, Professor and President of Sun Yat-sen University Cancer Center in Guangzhou, China, to talk about some of the ways that progress in cancer treatments had been made more productive by co-operation between Chinese and Western centers of oncology excellence.