Oncology Times - OncTimes Talk

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 transplant and spare those for whom the risk/benefit ratio is adverse.

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.