Oncology Times - Ot Broadcasts From The Ipad Archives

Patients with non-small cell lung cancer who have failed initial immunotherapy therapy with anti-programmed cell death ligand-1 (PDL-1) checkpoint inhibitors, have responded to a new “bispecific” antibody that targets both the programmed cell death-1 (PD-1) antibody and also the T-cell immunoglobulin and mucin domain 3 (TIM-3) molecule. Benjamin Besse, MD, PhD, Director of Clinical Research at the Department of Cancer Medicine in the Institut Gustave Roussy, Villejuif, Paris, reported a Phase 1/2a study—the first to be done in humans—at the European Society for Medical Oncology 2023 annual congress held in Madrid, Spain. OncTimesTalk correspondent, Peter Goodwin, interviewed Besse after the congress to find out about the potential clinical benefits the new drug AZD7789 (now called: sabestomig) among patients whose tumors have the TIM-3 target, and how—together with other targeted approaches— this bi-specific antibody could impact outcomes for an increasing proportion of patients with lung cancer.

Patients with high-risk prostate cancer who have been treated with radical prostatectomy gain no additional advantage and face extra toxicity if they choose to have adjuvant radiotherapy. That’s according to the findings of the randomized RADICALS study, reported at the 2023 annual congress of the European Society for Medical Oncology (ESMO) held in Madrid, Spain. These results support the use of early salvage radiotherapy for PSA failure after radical prostatectomy rather than early adjuvant intervention. After the conference OncTimes Talk’s Peter Goodwin travelled to Manchester, England, to discuss the RADICALS study with lead author Noel Clarke, MBBS, FRCS, ChM, FRCS, Chair of Urological Oncology at Manchester University and the Christie Hospital.

Research presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics found that a combination of two drugs targeting the nRAS mutation had clinical activity in patients with checkpoint-inhibitor refractory melanoma and had potential for treating other solid tumors with mutated nRAS as their oncogenic driver. Rodabe N. Amaria, MD, from the MD Anderson Cancer Center, Houston, talks with OncTimes Talk’s Peter Goodwin about her group’s Nautilus phase 1b/2 study that added an oral histone deacetylase inhibitor (HDACi), bocodepsin, to therapy with a mitogen-activated protein kinase enzyme (MEK) inhibitor, binimetinib, to target the RAS-pathway in solid tumors. The researchers found the combination of bocodepsin and binimetinib was tolerable in patients with RAS-mutated advanced cancers with manageable adverse events, and that this combination brought clinical responses indicating a potential benefit for patients who have failed immunotherapy.

<p>Among patients with non-small cell lung cancers driven by mutations in the epidermal growth factor receptor (EGFR), those with MET-amplification can now be selected for therapy with two tyrosine kinase inhibitor drugs, not just standard osimertinib. That&rsquo;s according to conclusions from the INSIGHT 2 study reported at the AACR-NCI-EORTC international conference on Molecular Targets and Cancer Therapeutics.</p><p>Presenting author Xiuning Le, MD, PhD, from the MD Anderson Cancer Center in Houston, Texas, has been talking with OncTimes Talk&rsquo;s Peter Goodwin about her group&rsquo;s study in which osimertinib was combined with the MET-tyrosine kinase inhibitor tepotinib in patients who tested positive for MET-amplification.</p>

Among patients with non-small cell lung cancers driven by mutations in the epidermal growth factor receptor (EGFR), those with MET-amplification can now be selected for therapy with two tyrosine kinase inhibitor drugs, not just standard osimertinib. That’s according to conclusions from the INSIGHT 2 study reported at the AACR-NCI-EORTC international conference on Molecular Targets and Cancer Therapeutics. Presenting author Xiuning Le, MD, PhD, from the MD Anderson Cancer Center in Houston, Texas, has been talking with OncTimes Talk’s Peter Goodwin about her group’s study in which osimertinib was combined with the MET-tyrosine kinase inhibitor tepotinib in patients who tested positive for MET-amplification.

The Chloride Intracellular Channel 1 (CLIC1) protein appears to hold the key to understanding the anti-proliferative action of metformin, according to laboratory evidence discussed at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held in October 2023, in Boston. At the conference, Michele M. Mazzanti, PhD, from the Department of Bioscience, at Milan University, Italy, reported his group’s recent findings about the possibility of using metformin to reduce glioblastoma mortality. Afterwards he discussed the study and its clinical implications with OncTimes Talk correspondent, Peter Goodwin.

Dr. Takahashi talks with OncTimes Talk’s Peter Goodwin about the Phase 2 study he presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, October 11 - 15, 2023. Dr. Takahashi reported an improvement in median overall survival among patients with relapsed small cell lung cancer who had the ATR inhibitor berzosertib added to standard topotecan.

Acute myeloid leukemia (AML) is notoriously difficult to treat. Only 28 percent of patients survive beyond 5 years after diagnosis. Mitophagy, a process in which damaged mitochondria are eliminated to prevent the transmission of death signals, has been identified as a key mechanism that allows leukemia cells to resist the effects of the widely prescribed drug venetoclax, according to a recent study published in Cancer Discovery and led by scientists from Perlmutter Cancer Center at NYU Langone Health. Today on OncTimes Talk, we interview Dr. Christina Glytsou, lead author of the study, and discuss the reasons behind leukemia cells’ resistance to venetoclax, a BH3 mimetic drug that promotes cancer cell death in individuals with AML. Dr. Glytsou holds a joint appointment as an Assistant Professor in the Department of Chemical Biology at the Ernest Mario School of Pharmacy of Rutgers University and the Department of Pediatrics at Rutgers Robert Wood Johnson Medical School. She is a member of Cancer Metabol

Some of the big randomized clinical trials could lead to unintentional bias because of an imbalance of assigned treatment discontinuations between experimental and control arms, according to ASCO poster author Faris Tamimi, MD, at the University Health Network Division of Medical Oncology and Hematology at Princess Margaret Cancer Centre. OncTimesTalk correspondent Peter Goodwin talked with Tamimi at the 2023 ASCO Annual Meeting.

Although T-DXd had already been licensed for use in all categories of HER2 positivity, including patients with so-called HER2-low tumors (defined as having immunohistochemical score of 1+ or 2+ with non-amplified in-situ hybridization), doubts have remained about the effectiveness of this antibody drug conjugate in the subset of such patients who also have low expression of the estrogen receptor, ER (having ER expression from 1-10%). At the ESMO Breast Cancer 2023 conference a sub-study analysis of the DESTINY-Breast04 Phase III study was reported that specifically addressed this topic. OncTimesTalk reporter, Peter Goodwin, asked David Cameron, MD, about his group’s findings on the effectiveness of T-DXd in ER-low metastatic breast cancer, and about the context and overall potential of using antibody drug conjugates in breast cancer. Cameron is Professor of Oncology at Edinburgh University and a joint lead for the Edinburgh Experimental Cancer Medicine Centre.

A mathematical study of real-world data from 27,855 women whose breast cancer was diagnosed between 2008 and 2020 has shown that a machine-learning artificial intelligence algorithm was able to predict mortality and could become a key weapon in the clinician’s armory when selecting therapies on the basis of predicted survival. Initial findings and conclusions from the study were reported at the European Society for Medical Oncology (ESMO) Breast Cancer Congress 2023. First author of the study, Laura Vuduc from the Department of Applied Mathematics at CentraleSupélec, Paris-Saclay University in Gif-sur-Yvette near Paris, France, talked about the importance of this new development with OncTimesTalk correspondent, Peter Goodwin.

Caution was expressed at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting about potential adverse effects from one form of breast cancer treatment de-escalation. A poster warns about risks from omitting axillary sentinel node surgery in older women.   In this edition of OncTimesTalk correspondent Peter Goodwin hears about axillary dissection in older women with clinically node-negative breast cancer from Mariam Rana, MD, FRCSC, Oncology Surgeon with the University of Saskatchewan in Canada College of Medicine, in discussion with Robert Hills, DPhil, Chair of Medical Statistics at Oxford University Nuffield Department of Population Health, who leads the secretariat for the Early Breast Cancer Trialists' Collaborative Group.   They discuss Rana’s ASCO poster that found the omission of axillary surgery to stage the axilla may be associated with a higher risk of overall mortality in older women with early-stage breast cancer, compared to those who have this surgery.

A real-world study reported at the ESMO Breast Cancer 2023 Annual Congress identified a risk for inappropriate therapeutic decision-making resulting from an alarmingly high rate of false-negative tests coming from biopsy specimens looking for biological parameters such as PR and HER2.  Study researchers at the University of Catania suggested tumor heterogeneity was a big reason why markers like PR and HER2 were being missed that subsequently turned up in surgical specimens. But biopsy technique was also an issue, they concluded. OncTimesTalk correspondent Peter Goodwin caught up with one of the study authors, Federica Martorana, Assistant Professor of Medical Oncology. Together with lead author Sabrina Nucera from the University of Messina, and their co-authors, she said they retrospectively analyzed data from samples—collected over a 10 year period—for which both biopsy and surgical specimens were available. They excluded patients receiving neoadjuvant therapy and looked for differences in t

Patients with breast cancer who complied fully with their adjuvant endocrine medication lived 15 percent longer than those who skipped doses, according to a huge real-world study coordinated from Tübingen University, in Baden-Württemberg, Germany, reported at the 2023 ASCO Annual Meeting. OncTimesTalk correspondent Peter Goodwin discusses the findings with senior author of the study, Dominik Dannehl, MD, a physician at the Department of Women's Health, Tübingen University Hospital, in Tübingen, Baden-Württemberg, Germany.

Being overweight or obese can reduce the benefit of extending adjuvant breast cancer hormone therapy in women younger than 60 years, according to research from the DATA trial discussed at the European Society for Medical Oncology (ESMO) Breast Cancer 2023 Congress. Senna W.M. Lammers, MD, from Maastricht University Medical Centre in The Netherlands, reported her findings from the DATA trial looking at the benefit of extending adjuvant hormonal therapy by treating women with hormone receptor-positive breast cancer who had already received tamoxifen with an additional course of anastrozole. The study confirmed an overall benefit in disease-free survival from extending the endocrine therapy, but also found this was impacted by body mass index: with overweight and obese patients benefiting less if they were under the age of 60.

Non-small cell lung cancer was one of the big topics at the 2023 ASCO Annual Meeting where Heather Wakelee, MD, FASCO, Professor of Medicine and Chief of the Division of Oncology at Stanford University in California, was overheard reminding a junior cancer doctor that the only adjuvant therapy for lung cancer had been chemotherapy just a couple of decades previously.  Now, a plethora of targeted therapies are available, and Wakelee reported a big improvement in outcome from one of them—pembrolizumab—used both before and after surgery in early Stage II and III disease (mostly Stage III). “These results indicate perioperative pembrolizumab given in combination with chemotherapy prior to surgery and for up to one year as a single agent after surgery led to significant improvement in event-free survival (defined by local progression precluding definitive surgery, recurrence, or death) with a strong trend towards improvement in overall survival. These results indicate peri-operative pembroli

End-of-life care for patients with cancer could be significantly improved while simultaneously reducing cost according to the findings of a study from the University of Pennsylvania. Ravi Parikh, MD, MPH, talks with OncTimesTalk correspondent Peter Goodwin about his findings on the value of harnessing AI to help doctors have serious illness conversations with patients during end-of-life care.

Roy Herbst, MD PhD, Deputy Director of the Yale Cancer Center at Yale School of Medicine, talks with OncTimesTalk correspondent Peter Goodwin about his group’s findings from the international Phase III ADAURA clinical trial looking at adjuvant therapy with the anti EGFR-mutant drug osimertinib in patients with completely resected stage one B to three A non-small cell lung cancer. In a late-breaking abstract reported at the 2023 American Society of Clinical Oncology Meeting Plenary Session, Herbst showed that osimertinib not only improved disease-free survival, but also brought a clear and big benefit in overall survival.

Roy Herbst, MD PhD, Deputy Director of the Yale Cancer Center at Yale School of Medicine, talks with OncTimesTalk correspondent Peter Goodwin about his group’s findings from the international Phase III ADAURA clinical trial looking at adjuvant therapy with the anti EGFR-mutant drug osimertinib in patients with completely resected stage one B to three A non-small cell lung cancer. In a late-breaking abstract reported at the 2023 American Society of Clinical Oncology Meeting Plenary Session, Herbst showed that osimertinib not only improved disease-free survival, but also brought a clear and big benefit in overall survival.

Progress in esophageal cancer is forging ahead at Columbia University in New York. Brian Henick, MD, is a medical oncologist specializing in the care of patients with malignancies of the aerodigestive tract. As Associate Director of Experimental Therapeutics and Director of Translational Research in Aerodigestive Cancers in Medical Oncology, Henick is involved in a wide range of studies at Columbia. Oncology Times correspondent Peter Goodwin recently had the opportunity to ask Henick about new therapy approaches for esophageal cancer, in particular molecular mechanisms and immunotherapies.