Oncology Times - OncTimes Talk

<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 Metabolism & Immunology and the Cancer Pharmacology Programs, at the Cancer Institute of New Jersey. Dr. Glytsou’s laboratory aims to address fundamental questions unravelling the role of mitochondrial biology in blood malignancies’ progression and drug resistance.

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 the detection of estrogen and progesterone receptors plus Ki67, as well as HER2 score, tumor grade, and intrinsic subtype. As a result, they had to re-classify 25 out of 61 cases of luminal B-like breast cancer that turned out mostly to be luminal A, with three of them being triple-positive.