Audio Journal of Oncology Podcast Audio Medica News

BRIGHTON, UK—In underserved communities throughout the world low rates of early breast cancer detection are key drivers of mortality, according to the findings of research from Uganda, the United Kingdom and Nigeria. A range of low cost community-based interventions could be used to modify these drivers, the research concludes.
Huge reductions of breast cancer mortality in underserved communities could be achieved by prioritizing early detection, according to lead author Deborah Ikhile PhD, from the Brighton and Sussex Medical School at the University of Brighton in Sussex UK, who discussed the implications of her findings with the Audio Journal of Oncology’s Peter Goodwin at the Royal Society of Medicine’s 2023 Tackling Inequalities conference.  This could be achieved—even where costly mass screening was not possible—by health education delivered through existing social and cultural structures that were presently being overlooked or ignored, her study concluded.
“Breast cancer is beyond an individual disease,” said Dr. Ikhile. “Doctors, researchers, clinicians, decision-makers need to have in-depth understanding of the social determinants that influence a woman’s ability to present early or not.”
Her group’s five-year survey with structured interviews among women in rural and semi-rural communities of Uganda had concluded that ‘structural violence’ was a root cause of late breast cancer detection.
This consisted of multiple disservices to women, unintentionally perpetrated through inappropriate medical care structures. Poor health education plus myopic national, global and donor priorities, all combined with negative attitudes to women, and a failure to engage with the well-established grass-roots local organizations in the community.
According to Dr. Ikhile, existing local services and social infrastructures could be harnessed to turn around breast cancer detection.
The present-day two-fold excess of mortality from breast cancer among most black African women everywhere (as compared their white counterparts in privileged communities) could largely be eliminated by effective early detection.  It was necessary to overcome factors such as stigma, misogyny, fear and gender prejudice from the global level downwards.  She believed Uganda was not exceptional and that the findings were relevant to cancer detection in underserved communities everywhere.
Dr. Ikhile’s interest in getting to the bottom of breast cancer inequalities began when she was still living in Nigeria and had (what turned out to be) a benign breast lump. Because she had access to private medicine her parents were able to get prompt diagnosis, followed by surgical excision. But this sensitized her to the plight of millions of women in low-resourced communities who did not have access to private health care.
The research in Uganda sought to identify the challenges and barriers to breast cancer detection and to investigate how these issues could be addressed within a primary care context.
The findings showed that cancer in Uganda was beyond individual control. “What came out is that, beyond your lack of knowledge, your lack of awareness, beyond fear, beyond attitude: Other factors, like community support, primary care services, even the clinician’s pressures, all these factors come into play, and support us to look at a holistic view to breast cancer detection,” Dr. Ikhile said. The survey also found that even after eventual detection of breast cancer there was often no easy access to follow-up care and services.
The whole agenda surrounding campaigns such as the Early Detection Saves Lives initiative had been flawed, as these had often centered around victim-blaming—making it seem as though the women were responsible for not detecting breast cancer early. But this was not a reality for most women, according to Dr. Ikhile. “The reality for women is th

Audio Journal of Oncology, February 14 2023, Reporting from the American Society of Hematology Annual Meeting (ASH), December 2022
An interview with Amy A. Kirkwood MSc, Senior Statistician at the Cancer Research UK & UCL Cancer Trials Centre, University College, London, UK
Interviewer: Peter M Goodwin
TITLE: Options Identified for in Acute Lymphoblastic Leukemia
NEW ORLEANS, USA—A big study conducted over an extended period of time has shown that there is scope for reducing the intensity of chemotherapy for patients with acute lymphoblastic leukema (ALL) and (the rarer) lymphoblastic lymphoma (LBL). Modifications to standard protocols offer scope for sparing many children the potential toxicity of full-does standard regimens without compromising cure rates.
Amy Kirkwood, Chief Statistician from University College, London tells the Audio Journal of Oncology (AJO) about her group’s findings from the randomized phase three UKALL 2011 study, reported (at the American Society of Hematology (ASH) 2022 Annual Meeting), showing that adjustments to current multi-agent chemotherapy regimens brought changes in outcome. She concludes that more gentle treatments may be possible for many patients while maintaining or improving efficacy for those at high risk.
https://ashpublications.org/blood/article/140/Supplement%201/516/488151/High-Dose-Methotrexate-Does-Not-Reduce-the-Risk-of
The treatment of ALL had improved hugely in the last 50 years, first author Amy A. Kirkwood MSc, Senior Statistician at the Cancer Research UK & UCL Cancer Trials Centre, University College, London, UK, told the AJO after giving her report at ASH. “We now have about 95 percent survival. About 15 percent of children will relapse. But we know that 50 years ago we were curing about 50 per cent of people with half the treatment. So, we know that we are overtreating large numbers of children,” she said.
So, trials were now looking at treatment reductions, and at trying to identify high-risk patients to design new ways of improving efficacy for that group only, she said. “We want to try and decrease treatment for the majority who will do well,” Kirkwood noted.
Specifically, the trial found that using high-dose methotrexate (HDM) did not improve central nervous system (CNS) relapse—contrary to some expectations. According to the UKALL 2011 study findings, it may have improved bone marrow relapse for some sub-groups of patients with B-lineage disease, however.
The trial also found that with some chemotherapy regimens the addition of monthly “pulses” of vincristine and dexamethasone (in the maintenance phase of treatment) had been un-necessary. They proved to be “non-inferior” for bone marrow relapse—compared with the standard practice of including such pulses. This suggested that pulse-free treatment could potentially be an option for some patients.
Study details
The UKALL 2011 study allocated patients to study arms in accordance with their risks, as stratified by National Cancer Institute (NCI) risk, cytogenetics and “end of induction minimum residual disease” (MRD). The aim was to assess whether elements of treatment could potentially be de-escalated without loss of efficacy. Randomizations were allocated within the several different standard “blocks” of chemotherapy.
Firstly, in the “induction” block of chemotherapy (aiming to get rid of most of the disease) there was a randomization between two different dose schedules of dexamethasone. A short (higher) dose schedule was compared with standard dexamethasone dosing. The aim had been to look at whether steroid dose could influence the incidence of side effects. This was followed by the “consolidation” block all in which all patients were treated the same.
Kirkwood said they saw no difference from steroid dosing schedule changes. “We were hoping to see a difference in steroid-related mo

Interview with Matthias Stelljes MD, Head of the Allogeneic Stem Cell Program at the University of Münster, Germany
NEW ORLEANS, USA—For your patients with acute myeloid leukemia (AML) the benefit of prompt allogeneic hematopoietic cell transplantation (alloHCT)  extends to those whose disease has relapsed or is refractory to induction therapy, and should not be delayed in favor of further intensive chemotherapy in an attempt to achieve a complete remission. That’s according to conclusions from the randomized phase three ASAP (As Soon As Possible) Trial, reported by German researchers at the American Society of Hematology (ASH) 2022 Annual Meeting.
https://ashpublications.org/blood/article/140/Supplement%201/9/488703/In-Patients-with-Relapsed-Refractory-AML
“Allogeneic stem cell transplantation is a very potent strategy which is curative for many patients,” said senior author of the study, Johannes Schetelig, Prof. Dr. med., at the University of Dresden in Germany. “Our study suggests that the international standard of bringing patients into remission first should be questioned, as it proves that allotransplant should be considered a standard treatment option even for patients with active disease.”
The new study was the first prospective randomized trial to assess whether or not high-dose “salvage chemotherapy” (to attempt to bring about a complete remission)  made a difference in long-term outcomes after a stem cell transplant. Patients whose AML had relapsed or who did not respond to initial chemotherapy had similar outcomes when they proceeded directly to alloHCT compared with those who underwent intensive chemotherapy in the attempt to achieve complete remission first.
Retrospective data had established that having a complete remission prior to allogeneic hematopoietic cell transplantation was indeed a favorable risk factor for patients with AML. But the ASAP Trial had been the first to examine this relationship prospectively, the researchers noted.
“We were astonished. We never expected these results,” Schetelig said. “Patients did not gain additional benefit from salvage chemotherapy at all. It suggests we should think about starting the process of allotransplantation as soon as possible.”
In previous phase two trials the researchers had found transplanting patients who had active disease brought a benefit. “We had some good experience in the past where we were able to successfully treat patients with an allogeneic stem cell transplantation even in the setting of active disease,” said first author of the ASAP study, Matthias Stelljes MD, Head of the Allogeneic Stem Cell Program at the University of Münster, Germany.
Stelljes acknowledged that the majority of centers did not usually perform alloHCT in patients with relapsed or refractory AML with active disease. The new findings from ASAP, however, ran counter to the common practice of offering prompt transplantation only to patients who were in complete remission and clearly imply that many patients could skip the additional step of having salvage chemotherapy before receiving a transplant.
The study enrolled 281 patients treated for relapsed or refractory AML in Germany. Half of them were randomized to proceed directly to alloHCT and remaining half had salvage chemotherapy first. The median time from randomization to transplant was four weeks among those proceeding directly to a transplant and eight weeks among those receiving salvage chemotherapy first. Researchers tracked outcomes for a median of just over three years.
In the standard arm patients had salvage therapy with high dose cytarabine (ara-C) and mitoxantrone and then received an allogeneic transplant. This was either in subsequent remission or with active disease in those in whom no remission could be achieved, Stelljes told the Audio Journal of Oncology. “In the experimental arm we did not perform any salvage tre

Ibrutinib Enables Transplant-Free Therapy for Mantle Cell Lymphoma
NEW ORLEANS, USA—Many patients eligible for autologous stem cell transplantation for their mantle cell lymphoma (under current best practice recommendations) could be treated as effectively—and potentially with less toxicity—with the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, according to findings from Munich, Germany.
The Randomized Triangle Trial, conducted by the European Mantle Cell Lymphoma Network, reported positive findings about a transplant-free approach to the American Society of Hematology 2022 Annual Meeting.
https://ashpublications.org/blood/article/140/Supplement%201/1/490022/Efficacy-and-Safety-of-Ibrutinib-Combined-with
Audio Journal of Oncology correspondent Peter Goodwin talked with study leader Martin Dreyling MD PhD, Professor of Medicine at LMU (Ludwig Maximilian University) Hospital in Munich, Germany about their findings that strongly suggest standard chemotherapy plus ibrutinib (with or without autologous stem cell transplantation) should be the new first-line standard of care for patients with mantle cell lymphoma.
Toxicity
But the German team also noted that the high efficacy of chemotherapy brought high toxicity rates. So, they compared the standard induction (with a cytarabine-containing regimen plus autologous transplant and rituximab maintenance) with two experimental arms, said Dreyling. “One was a simple add-on design—which means ibrutinib [was] added to [standard] induction and maintenance. And the third arm was even more interesting: substituting for autologous transplant.”
“The add-on design resulted in a significant improvement of progression free survival—around 15 per cent after three years: in my opinion highly clinically relevant,” he said. Also, the study found that a group of difficult-to-treat patients—those whose tumors had p53 gene alterations—had specifically benefited from the addition of ibrutinib.
Patients who took the targeted drug ibrutinib had rates of failure-free survival (FFS) and overall survival (OS) that were similar to the current standard of care—whether or not they received a stem cell transplant in addition to ibrutinib. Those treated with ibrutinib who did not have ASCT had significantly lower rates of toxicity. And in the arm in which ibrutinib was added to transplantation, the toxicity was no higher than among patients treated with standard of care, the study found.
“We are moving away from intensive chemotherapy to [a] targeted approach. The new standard of care in younger patients is still a combination of chemo plus ibrutinib. The future, I hope, will be skipping chemotherapy [altogether] and moving to a purely targeted approach—hopefully leading to better outcomes, but definitely better tolerability of our treatment regimens,” Dreyling told OT.
Study details
The trial enrolled 870 adult patients up to 65 (median age 57 years) treated for MCL in 13 European countries and Israel. All patients were eligible for ASCT. 288 of them (group A) were assigned to receive standard care (high-dose cytarabine-containing immunochemotherapy followed by ASCT and rituximab maintenance). 292 patients (group A + I) were treated with the same standard care plus ibrutinib, and 290 patients received ibrutinib without having a transplant (group I).
Transplant not superior
After a median follow-up of 31 months, group A failed to show superiority over group I in terms of FFS (three-year FFS was 72 per cent compared with 86 per cent in group I (p=0.9979, hazard ratio: 1.77). In group A+I, the FFS was superior to group A: 88 per cent compared with 72 per cent in group A (p=0.0008, hazard ratio: 0.52). OS was 86 per cent in group A, 91 per cent in group A+I, and 92 per cent in group I.
Toxicities
The study found no substantial differences in the incidence of grade three to five adverse events (AEs) during induction wi

January 10, 2023
Fast Durable Responses to Bi-Specific Antibody Therapy In Heavily Pre-Treated Multiple Myeloma
INTERVIEW WITH:
Ajai Chari MD, Associate Professor of Medicine and Director of Clinical Research in the Multiple Myeloma Program at Mount Sinai School of Medicine in New York, USA.
NEW ORLEANS, USA—The bispecific antibody talquetamab, classed as a “T-cell redirecting therapy” achieved high response rates in the phase one/two multi-national MonumenTAL-1 study investigating 288 patients who had heavily pre-treated refractory multiple myeloma.
Findings reported at the American Society of Hematology 2022 Annual Meeting showed that nearly three-quarters of patients treated had “complete” or “very good partial” responses within one or two months, and median response durations of around nine months.https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.8015
“Remarkably in this unmet need we saw response rates of 73 to 74 per cent. The responses were maintained in triple-class refractory patients, penta-drug refractory patients, ISS (International Staging System) three high-risk disease,” said Ajai Chari MD, Associate Professor of Medicine and Director of Clinical Research in the Multiple Myeloma Program at Mount Sinai School of Medicine in New York, USA.
“The median time to response was one month—which is outstanding. And the median time to “best response” was slightly over two months—which is great, because it means that these patients who had explosive disease (these are not CAR-T cherry-picked patients with really indolent progression) were benefiting in high percentages—and quickly, and deeply,” Chari told the Audio Journal of Oncology.
Although patients with extra-medullary disease had fared slightly less well, their responses had still been good, he said. “Even there, there was an impressive 50 per cent response rate.”
Talquetamab was an off-the-shelf bispecific antibody, that binds to both T cells and multiple myeloma cells, said Chari. This facilitates an immune response to destroy myeloma cells by bringing T cells to the cancer. Its twin targets were the CD3 T-cell receptors and the cancer cell surface receptor known as G protein-coupled receptor family C group 5 member D (GPRC5D).
“[Previously] we only had naked antibodies. And a bispecific antibody is different. Like with all antibodies it has the Y-shaped structure, but unlike typical antibodies it binds two different targets.  One target is the T cell—with CD3; and the other target is GPRC5D, which is a novel target in myeloma. It’s over-expressed particularly on malignant plasma cells, less so on normal plasma cells, and—importantly—not on the hematopoietic stem cell compartment—Which we think is a favorable finding,” said Chari.
“You basically can engage the patient’s own T-cells to try to attack the myeloma. And it’s a little surprising how remarkable this whole approach has been: Because patients with myeloma who are entering these studies have typically five to six lines of therapy over six years, are usually in their late sixties [or] early seventies, and you wouldn’t think that their T-cells would even be robust, and fit, and present, enough to generate results—let alone the outstanding results we’re seeing,” he said.
In the MonumenTAL-1 study, patients with relapsed/refractory multiple myeloma, were treated with either of two recommended dosing regimens: 0.40 mg/kg of talquetamab subcutaneously at weekly intervals, or 0.80 mg/kg every other week.
Results
Patients in the weekly and bi-weekly dose regimens (equivalent in overall dose intensity) had similar outcomes in terms of response rates and toxicities. Nearly a third of patients had complete responses. More than half had “very good” partial responses. The responses deepened with time, and conti

An interview with: Byoung Chul Cho MD PhD, Thoracic Medical Oncologist, from the Yonsei Cancer Center at Yonsei University College of Medicine in Seoul, South Korea.
BARCELONA, Spain—A “next generation” ROS1 tyrosine kinase inhibitor (TKI), repotrectinib—studied in the phase one/two Trident-1 study among patients whose advanced non-small cell lung cancers (NSCLC) had tested positive for the ROS1 fusion protein receptor tyrosine kinase (encoded by the ROS1 oncogene)—resulted in high response rates with low toxicities, according to results reported at the 2022 European Organisation for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research (EORTC-NCI-AACR) Symposium on Molecular Targets and Cancer Therapeutics.
Byoung Chul Cho discusses the trial and its clinical implications for patients with ROS1 positive NSCLC (one or two per cent of all lung cancer cases).
Among the study patients treated at 150 hospitals around the world, some had never been treated with a ROS1 TKI, some had already been treated with one ROS1 TKI, some had been treated with a ROS1 TKI and platinum-based chemotherapy, and some had been treated with two different ROS TKIs. As of June 20, 2022, the primary efficacy population had included 71 TKI-naive patients and 56 TKI-pretreated patients with no prior chemotherapy.
 “In TKI-naïve patients repotrectinib showed a 78 per cent objective response rate (tumor reduction of at least 30 per cent) and the 12 months duration of response was 86 per cent,” said Cho after his late breaking session at the Symposium. In the patients who had no prior chemotherapy who had been treated with a previous-generation ROS1 TKI he said they also found a good response rate. “Repotrectinib showed a 37 per cent objective response rate with a six months duration of response [of] 79 per cent,” he said.
A significant issue with ROS1 TKI treatment had been that patients usually developed the so-called G2032R resistance mutation that rendered further TKI therapy ineffective. “The G2032R resistance mutation is the most common resistance mechanism,” said Cho. “Repotrectinib showed objective response rate of 58 per cent in this population.”
Anti mTrk activity
Another putative advantage for the investigational agent in Trident-1 had been that it also inhibited mutated tropomyosin receptor kinase receptor (Trk: usually pronounced “track”) a molecular feature often found in association with ROS1. “So, in the Trident-1 trial we also evaluated the activity and safety of repotrectinib in m-Trk fusion-positive solid tumors in both TKI naïve and TKI pretreated populations,” Cho said. A phase one study by Besse and colleagues from Villejuif, France—working on Trident-1 in collaboration with Cho and others—had already found that repotrectinib demonstrated efficacy in TKI-naïve and TKI-pretreated patients and was generally well tolerated.
https://aacrjournals.org/mct/article/20/12_Supplement/P02-01/675917/Abstract-P02-01-Repotrectinib-in-patients-with
Brain metastases
When Cho was asked about the impact of the new TKI on cranial metastases he said the drug had been effective. “CNS metastasis is one of the commonest sites of metastasis after progression on a ROS1 TKI. In this study we [observed] a very high intracranial activity of repotrectinib in both TKI naïve and TKI pre-treated populations.” Nearly 90 per cent of the small number of patients with measurable tumors in the brain not previously treated with a ROS1 TKI had intracranial objective responses (iORR). Just less than half of those already treated with one prior ROS1—and half of those treated with one prior ROS1 TKI and chemotherapy—had iORR. But none of the patients pre-treated with both chemotherapy and a TKI had responded.
Cho said that repotrectinib had been generally well tolerated. “The most com