Oncology Times - Ot Broadcasts From The Ipad Archives

A new targeted drug, revumenib, was found to increase response rates and survival in patients whose previously treated acute leukemias relapsed or were refractory to treatment. A Phase II clinical study found revumenib met its primary endpoint and was stopped early because of a high patient response rate and clinical efficacy. Revumenib acts on the hitherto untargeted histone-lysine N-methyltransferase 2A (KMT2A)-rearranged gene, which is present in around 1 in 10 acute leukemias among patients of all ages. The drug inhibits the interaction of the protein menin (associated with tumor suppression) and the KMT2A-fusion protein, which is believed to be an oncogenic driver in leukemias. OncTimesTalk correspondent Peter Goodwin heard the latest from lead study author Ibrahim Aldoss, MD, Associate Professor in the Division of Leukemia of the Department of Hematology & Hematopoietic Cell Transplantation at the City of Hope, after his report to the 65th ASH Annual Meeting & Exposition.

A marked improvement in the outlook for patients with locally advanced cervical cancer has been achieved thanks to a neoadjuvant regimen using standard anti-cancer drugs added to usual therapy.  At the ESMO Congress 2023 held in Madrid, Spain, Mary McCormack, PhD, MBBS, FRCR, Consultant Clinical Oncologist at University College London Hospitals, reported findings from the GCIG INTERLACE randomized Phase III trial of induction chemotherapy. This involved the use of carboplatin with paclitaxel for 6 weeks immediately before standard chemoradiotherapy. After the conference, OncTimesTalk’s correspondent Peter Goodwin visited McCormack to find out more about the clinical implications arising from the INTERLACE study.

Patients whose advanced non-small cell lung cancers harbor the RET gene fusion should receive initial treatment with the RET-targeted agent selpercatinib rather than chemotherapy or chemotherapy combined with immunotherapy. This clear message comes from the randomized Phase III LIBRETTO-431 study reported at ESMO Congress 2023 by Herbert Ho Fung Loong, MBBS, FRCP, Associate Professor in the Department of Clinical Oncology at The Chinese University of Hong Kong in China. After his talk in Madrid, OncTimesTalk correspondent Peter M. Goodwin talked with him about the study findings and clinical implications, as well as selpercatinib’s role in the landscape of cancer treatments along with other targeted therapies, chemotherapy, and immunotherapy.

The preferred first-line treatment for patients with uncommon sensitizing mutations in tumor epidermal growth factor receptor (EGFR) should now be the tyrosine kinase inhibitor (TKI) afatinib, rather than osimertinib, according to Japanese researchers reporting the ACHILLES trial results at the ESMO Congress 2023 held in Madrid. OncTimesTalk correspondent Peter Goodwin talked with Satoru Miura, MD, from the Niigata Cancer Center Hospital in Japan, after he reported his findings at the ESMO meeting.

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 ESMO Congress 2023. These results support the use of early salvage radiotherapy for PSA failure after radical prostatectomy rather than early adjuvant intervention. After the conference, OncTimesTalk’s Peter M. Goodwin travelled to Manchester, England, to discuss the RADICALS study with lead author Noel Clarke, MBBS, FRCS, ChM, Chair of Urological Oncology at Manchester University and the Christie Hospital in Manchester.

Although immunotherapies for patients with solid tumors such as melanoma can be dramatically successful, the majority of patients are resistant and require alternative treatments. While the cytokine interleukin-12 is well known for potentiating the effect of immunotherapies, such as checkpoint blockade, it couldn’t be used because of toxicity. At the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Jun Ishihara, PhD, a lecturer at London’s Imperial College reported on a protein bioengineering approach in which IL/12 is bound to collagen from the extracellular matrix of the tumor. This targets the cytokine’s action to operate specifically on cancer while hopefully avoiding most of the off-target toxicities previously observed with unbound IL/12.  After the conference, OncTimesTalk’s Peter Goodwin called to see him at his London laboratory.

The process of identifying which patients with acute myeloid leukemia (AML) can benefit from allogeneic stem cell transplantation in first complete remission (CR1) has taken a step forward thanks to analysis of the UK NCRI AML17 and AML19 studies, reported at the 65th ASH Annual Meeting and Exposition. Patients who achieved molecular residual disease (MRD) negativity in their peripheral blood were at low risk of relapse, and had no benefit from allogeneic transplant in CR1, including those with the FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication mutation of the NPM1 (nucleophosmin 1) gene, that is generally considered to be a marker of poor risk. Peter Goodwin spoke with Jad Othman, MBBS, from King's College London and the Guy's and St Thomas' Hospital in London, and now based at the Royal North Shore Hospital in Sydney, Australia. Othman explained how testing for the FLT3 mutation of the NPM1 gene can be used along with assessment of molecular MRD to help choose patients who can benefit from tr

With no standard-of-care treatment for patients with high-risk relapsed/refractory follicular lymphoma, promising remissions have been observed in a Phase II study reported at the 65th ASH Annual Meeting and Exposition. The antibody-drug conjugate loncastuximab tesirine in combination with rituximab brought a very high complete metabolic response rate among patients satisfying the criteria for high risk, including relapse within 24 months. After talking at the ASH meeting, first author Juan Pablo Alderuccio, MD, Associate Professor of Medicine in the Sylvester Comprehensive Cancer Center’s Division of Hematology at the University of Miami School of Medicine, discussed his findings with OncTimesTalk correspondent Peter Goodwin.

Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have poor outcomes after the failure of covalent Bruton's tyrosine kinase (BTK) inhibitor treatment, and new therapeutic options are needed. Pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor, was designed to re-establish BTK inhibition.

In a multinational, Phase III, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary endpoint).

Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking.

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.