A 30-year-long population-based study, reported at the 14th European Breast Cancer conference held in Milan, Italy, showed that breast-conserving therapy for ductal carcinoma in situ (DCIS) had become increasingly effective in preventing the emergence of breast cancer over the long term, but that there were still unanswered questions.

The population-based Netherlands Cancer Registry retrospective cohort study of 25,719 women with DCIS diagnosed from 1989 up to 2021 (all of whom were treated with standard conservative therapy) found there were successes and limitations with the current standard of care for DCIS.

Surprisingly, long-term risk appeared to have been unrelated to tumor grade. Also, despite a continuing improvement in outcomes during this period, the investigators concluded that specific molecular predictors of outcome still needed to be identified to distinguish intrinsically low-risk tumors (that did not require even conservative therapy) from those that carry higher risk and are highly likely to benefit from breast-conserving surgery and radiotherapy.

After reporting the study findings in Milan, study author Adri Voogd, PhD, Associate Professor of Clinical Epidemiology in the Faculty of Health, Medicine, and Life Sciences at Maastricht University, Maastricht, The Netherlands, discussed their clinical implications with Peter Goodwin.

Most patients whose breast cancer has spread to more than three lymph nodes can nevertheless be spared extensive axillary dissection, according to the findings of a study presented at the 2024 European Breast Cancer Conference in Amsterdam, The Netherlands.

Annemiek van Hemert, a Medical Doctor and PhD candidate at the Surgical Oncology Department of the Antoni van Leeuwenhoek-Netherlands Cancer Institute in Amsterdam, The Netherlands, reported her findings from a study using the MARI protocol (marking axillary lymph nodes with radioactive iodine seeds) that predicts cancer outcomes. The protocol was developed at the AVL Hospital in 2014 and is now being used in several Dutch hospitals.

After her session at the Milan conference, van Hemert talked with OncTimesTalk correspondent Peter Goodwin about the clinical implications of her group’s findings.

Artificial intelligence is being harnessed by a team of researchers at Leicester University in the United Kingdom to predict the risk of lymphedema (and potentially other toxicities) from the use of postoperative radiation therapy for breast cancer.

The 2024 European Breast Cancer Conference heard the latest news on an artificial intelligence tool that promises to help cancer clinicians individualize radiotherapy regimens after surgery to minimize toxicity.

Tim Rattay, MBChB, PhD, Associate Professor in Breast Surgery in the Leicester Cancer Research Centre at the University of Leicester and Consultant Breast Surgeon at the University Hospitals of Leicester in the UK, told the conference about his group’s machine-learning algorithm, PRE-ACT (Prediction of Radiotherapy side Effects using explainable AI for patient Communication and Treatment modification), that predicts post-operative lymphedema.

After reporting his research in Milan, Rattay called into the OncTimesTalk studio to give Peter Goodwin the details.

New data from the Phase III KEYNOTE-756 clinical trial show that adding pembrolizumab immunotherapy to chemotherapy before and after surgery for high-risk breast cancer (which was estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative) resulted in better outcomes for patients regardless of their age or menopausal status.

The findings were presented at the 14th European Breast Cancer Conference by KEYNOTE-756 study co-author Heather McArthur, MD, MPH, Clinical Director of the Breast Cancer Program and Komen Distinguished Chair in Clinical Breast Research at the UT Southwestern Medical Center. She reported the findings at the Milan conference on behalf of her co-author Javier Cortés MD, Head of the International Breast Cancer Centre in Barcelona, Spain.

After her talk in Milan, McArthur called into the OncTimesTalk Studio to talk about the findings with Peter Goodwin.

Offering MRI-guided partial breast irradiation before surgery to patients with low-risk breast cancer could become the norm, according to Yasmin Civil, MD, in the Department of Radiation Oncology at the Amsterdam UMC in the Netherlands, who reported 5-year results from the ABLATIVE trial to the 14th European Breast Cancer Conference.

The researchers found that single-dose, MRI-guided, partial breast irradiation given before breast-conserving surgery achieved durable pathologic complete remissions in low-risk breast cancer, as well as held out the prospect of surgery-free treatment for some patients. 

After giving her talk in Milan, Civil discussed the details of the ABLATIVE study findings with Peter Goodwin.

Adding checkpoint inhibition immunotherapy to adjuvant chemotherapy did not improve survival among patients with triple-negative breast cancers.

 

These findings from a study reported at the 14th European Breast Cancer Conference were presented by Heather McArthur, MD, MPH, Clinical Director of Breast Cancer and Komen Distinguished Chair in Clinical Breast Research at the University of Texas Southwestern Medical Center.

 

After McArthur’s talk in Italy, she shared the details with Peter Goodwin, OncTimesTalk correspondent.

About a quarter of all patients with newly diagnosed triple-negative breast cancer will not benefit from neoadjuvant checkpoint inhibitor immunotherapy with an agent such as pembrolizumab—even though it improves outcomes among the remaining majority.

 

At the 14th European Breast Cancer Conference, held in Milan, Italy, Laura van ’t Veer, PhD, Program Leader of the Breast Oncology Program at the UCSF Helen Diller Family Comprehensive Cancer Center, reported findings from the I-SPY2 TRIAL showing that analysis of “response predictive subtypes” identified a subset of patients with triple-negative early-stage breast cancers with a very low likelihood of response to neoadjuvant immunotherapy and can be spared potential toxicities.

 

After her talk in Milan, van ’t Veer called in to the OncTimesTalk studio to talk about the I-SPY findings with Peter Goodwin. 

An early study of patients (Phase I/II) with acute myeloid leukemia found that a new three-drug combination therapy greatly improved outcomes—both in patients with relapsed or refractory disease and as initial therapy. 

The new research involved adding quizartinib that targets fms-related tyrosine kinase 3 (FLT3) oncogene. Mutations of FLT3 are present in nearly a third of all AML tumors. The internal tandem duplication mutation of FLT3, in particular, is associated with poor prognosis in AML. So, it was hypothesized that targeting FLT3 could help in treating FLT3-mutated AML.

First author Musa Yilmaz MD, Associate Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, has been talking with OncTimesTalk correspondent Peter Goodwin. 

How best to treat patients with relapsed or refractory mantle cell lymphoma has been made clearer by a report from the multinational Phase III Sympatico Study, presented at the 65th ASH Annual Meeting and Exposition held in San Diego. Lead author Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at the University of Texas MD Anderson Cancer Center in Houston, told the conference how a combination of two targeted drugs—ibrutinib and venetoclax—improved outcomes.

2024 is the 20th year of clinical studies conducted as part of the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trial, a series of investigational approaches to initial therapy for patients with high-risk prostate cancer. Patient accrual has now ended, but practice-changing data continue to emerge from STAMPEDE. New agents, regimens, and optimized treatment combinations have been assessed in patients whose tumors already metastasized or were localized but judged highly likely to progress.

 

Noel Clarke, MBBS, FRCS, ChM, FRCS (Urol), Consultant Urological Surgeon and Professor of Urological Oncology at the Christie at Salford Royal Hospitals in Manchester, said the study is a multi-arm, multi-stage trial in which the current standard of care has continually been compared during the past 20 years with various candidate interventions tested against it. 

 

“Multiple thousands of patients have taken part in the trial,” Clarke said. “It has changed the standard of care serially in the last decade and has given a fantastic body of clinical and scientific material to work on, which helps us to understand prostate cancer, its natural history, the effect of different treatments, and the biology of prostate cancer, helping us to design future treatments.”

 

OncTimesTalk correspondent Peter Goodwin met up with Professor Clarke at his office in Manchester, England, and asked him about findings and clinical take-home messages that have come out of the STAMPEDE studies. They also discussed translational research the investigators are now conducting in their ongoing battle to fight prostate cancer.

The multicenter RAMOSE randomized clinical trial has found that doublet growth factor tyrosine kinase inhibitor therapy, when compared with standard osimertinib monotherapy, achieved a statistically significant improvement in progression-free survival in patients whose advanced non-small cell lung cancers were driven by mutated epidermal growth factor receptor.

First author Xiuning Le, MD, PhD, Associate Professor in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center, has been discussing her group’s findings with Peter Goodwin, an OncTimesTalk correspondent.

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 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.