Latest news with #NicholasTurner
Medscape
05-06-2025
- Business
- Medscape
Catching Resistance Early: Can New Breast Cancer Drug Help?
CHICAGO — Can spotting an emerging ESR1 mutation early and changing first-line drugs before progression improve outcomes in patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2–negative advanced breast cancer? Interim findings from the SERENA-6 trial suggest that may be the case. Patients who switched from a first-line aromatase inhibitor to camizestrant, an investigational next-generation oral selective estrogen-receptor degrader, at the first signs of an emerging ESR1 mutation demonstrated significantly improved progression-free survival compared with those who continued their initial regimen. Notably, circulating tumor DNA (ctDNA) testing allowed investigators to identify ESR1 mutations, which emerge at the time of disease progression in about 40% of patients on a first-line aromatase inhibitor and lead to treatment resistance. Camizestrant, which has shown activity in patients who develop ESR1 mutations, helped improve first-line outcomes and has 'potential to become a new treatment strategy,' according to co-principal investigator Nicholas Turner, MD, PhD, professor and honorary consultant in medical oncology at the Institute of Cancer Research and Royal Marsden Hospital, London, England, who presented the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting. Results were simultaneously published in The New England Journal of Medicine . This trial also demonstrated 'the clinical utility of ctDNA monitoring to detect and treat emerging resistance in breast cancer,' said Turner. While praising the findings, others were not convinced that the SERENA-6 results warrant a change in practice yet. 'Based on first-line progression-free survival alone, this could represent a new regulatory approval path,' said invited discussant Angela DeMichele, MD, of the University of Pennsylvania, Philadelphia. But, DeMichele cautioned, 'I cannot recommend the SERENA-6 strategy at this time.' One key reason, DeMichele noted, is that it's too early to tell whether this strategy improves overall survival. If camizestrant is approved based on progression-free survival and quality of life, DeMichele wondered, is it worth going through the ctDNA testing process if the drug doesn't help patients live longer? Paolo Tarantino, MD, a breast oncologist at Dana-Farber Cancer Institute and Harvard Medical School in Boston, echoed this sentiment in a tweet on X: 'Outstanding results, though not ready for clinical practice (yet),' adding that it will also be 'important to take into account financial, psychological, and systemic costs of the strategy.' Using ctDNA to Track Resistance In the study, 3256 patients who had received at least 6 months of treatment with aromatase inhibitors and CDK4/6 therapy (palbociclib, ribociclib, or abemaciclib) received ctDNA testing with Guardant360 CDx every 2-3 months at the time of routine staging exams. Overall, 315 patients who had an ESR1 mutation detected and had no radiologic evidence of disease progression were randomly assigned to either switch from the aromatase inhibitor to 75 mg of camizestrant daily (n = 157) or continue their aromatase inhibitor/CDK4/6 regimen (n = 158). (An additional 233 patients who had an ESR1 mutation detected were not included for a variety of reasons, including disease progression and consent withdrawal.) At the planned interim analysis, the median progression-free survival was 16.0 months in the camizestrant group and 9.2 months in the aromatase inhibitor group (adjusted hazard ratio [aHR], 0.44; P < .00001). At 24 months, only 5.4% of patients who had continued their initial first-line treatment had not progressed compared with 30% of patients on camizestrant. The progression-free survival findings were consistent across clinically relevant patient subgroups. Patients who switched to camizestrant also showed improved time to deterioration in global health status and quality of life — a median of 23.0 months vs 6.4 months in the aromatase group (aHR, 0.53). At the time of the interim analysis, overall survival data were immature, with 20 deaths in the camizestrant group and 19 in the aromatase inhibitor group (HR, 0.91; 95% CI, 0.48-1.73). As for time to second progression, there were 38 events in the camizestrant group and 47 events in the aromatase group, but the findings were also immature. As for adverse events, 60% of patients in the camizestrant group had a grade 3 or higher event, 10% of which were deemed serious compared with 46% in the aromatase group, 12% of which were serious. Neutropenia (45% vs 34%, respectively) and anemia (5% in both groups) were the most common grade 3 or higher adverse events. Only 1% of patients on camizestrant discontinued treatment due to adverse events. Overall, Turner concluded that 'for people with HR-positive advanced breast cancer, the results of SERENA-6 show that camizestrant plus CDK4/6 inhibitor could be a new treatment option to use at the point of ESR1 mutation detection during treatment with first-line aromatase inhibitor plus CDK4/6 inhibitor — but before the cancer grows.' Despite the promising findings, DeMichele highlighted several key unanswered questions and challenges. Notably, will this strategy lead to longer overall survival and demonstrate clinical utility? Overall survival and time to second progression are currently not known, DeMichele said. The trial did not address whether first-line treatment gains would be lost if camizestrant was given in the second-line setting after anatomic progression. DeMichele also noted the high cost and potential anxiety associated with serial ctDNA testing. Overall, 'the full complement of financial, psychological, and systemic costs is needed to fully assess utility and feasibility for implementation,' she added. SERENA-6 was supported by AstraZeneca. Turner disclosed consulting or advisory roles with AstraZeneca, Exact Sciences, Gilead Sciences, GlaxoSmithKline, Guardant Health, Inivata Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Relay Therapeutics, Repare Therapeutics, and Roche. DeMichele disclosed a consulting or advisory role with Pfizer.
The Sun
01-06-2025
- Business
- The Sun
Three-drug treatment combo ‘holds back aggressive breast cancer for a year'
A NEW triple threat drug combination could hold aggressive breast cancer at bay for an extra year, a trial found. Adding the medicine inavolisib to an already used pair of drugs delayed the need for chemotherapy by almost two years. 1 It prevented tumours from growing for an average of 17 months, compared to seven months in patients using the standard drug pairing palbociclib and fulvestrant. An estimated 1,000 British women per year could benefit. The combo works for women with a specific breast cancer type called HR+ HER2- with a PIK3CA mutation, which accounts for about three in 10 cases. Professor Kristian Helin, chief of The Institute of Cancer Research in London, said: 'We need to tackle treatment resistance head-on to continue improving survival rates. 'This triple combination approach effectively shuts down cancer's escape routes, giving people with metastatic breast cancer the opportunity to live well for longer.' The trial included 325 patients with aggressive and advanced breast cancer from 28 countries. Cancers shrank in two thirds of people receiving the triple drug combination, compared to 28 per cent of those on standard treatment. New go-to option for docs Study author Professor Nicholas Turner, of the Royal Marsden NHS hospital in London, said: 'This therapy not only helped patients live longer but it more than doubled the time before their cancer progressed or worsened. 'It also gave them more time before needing chemotherapy which is something that patients really fear and want to delay for as long as possible.' 'These results give us confidence that this treatment could become the new go-to option.' The study was presented at the conference of the American Society of Clinical Oncology. What are the signs of breast cancer? BREAST cancer is the most common type of cancer in the UK. The majority of women who get it are over 50, but younger women and, in rare cases, men can also get breast cancer. If it's treated early enough, breast cancer can be prevented from spreading to other parts of the body. Breast cancer can have a number of symptoms, but the first noticeable symptom is usually a lump or area of thickened breast tissue. Most breast lumps aren't cancerous, but it's always best to have them checked by your doctor. You should also speak to your GP if you notice any of the following: a change in the size or shape of one or both breasts discharge from either of your nipples (which may be streaked with blood) a lump or swelling in either of your armpits dimpling on the skin of your breasts a rash on or around your nipple a change in the appearance of your nipple, such as becoming sunken into your breast Source: NHS
Scottish Sun
01-06-2025
- Health
- Scottish Sun
Three-drug treatment combo ‘holds back aggressive breast cancer for a year'
The treatment could benefit thousands of British women Click to share on X/Twitter (Opens in new window) Click to share on Facebook (Opens in new window) A NEW triple threat drug combination could hold aggressive breast cancer at bay for an extra year, a trial found. Adding the medicine inavolisib to an already used pair of drugs delayed the need for chemotherapy by almost two years. Sign up for Scottish Sun newsletter Sign up 1 Breast cancer gets harder to treat as cells become resistant to drugs (stock image) Credit: Getty It prevented tumours from growing for an average of 17 months, compared to seven months in patients using the standard drug pairing palbociclib and fulvestrant. An estimated 1,000 British women per year could benefit. The combo works for women with a specific breast cancer type called HR+ HER2- with a PIK3CA mutation, which accounts for about three in 10 cases. Professor Kristian Helin, chief of The Institute of Cancer Research in London, said: 'We need to tackle treatment resistance head-on to continue improving survival rates. 'This triple combination approach effectively shuts down cancer's escape routes, giving people with metastatic breast cancer the opportunity to live well for longer.' The trial included 325 patients with aggressive and advanced breast cancer from 28 countries. Cancers shrank in two thirds of people receiving the triple drug combination, compared to 28 per cent of those on standard treatment. New go-to option for docs Study author Professor Nicholas Turner, of the Royal Marsden NHS hospital in London, said: 'This therapy not only helped patients live longer but it more than doubled the time before their cancer progressed or worsened. 'It also gave them more time before needing chemotherapy which is something that patients really fear and want to delay for as long as possible.' 'These results give us confidence that this treatment could become the new go-to option.' The study was presented at the conference of the American Society of Clinical Oncology. Breast cancer symptoms you should NEVER ignore, with Dr Philippa Kaye
Yahoo
01-06-2025
- Business
- Yahoo
AstraZeneca drug could help keep a common breast cancer at bay
This story was originally published on BioPharma Dive. To receive daily news and insights, subscribe to our free daily BioPharma Dive newsletter. Too often, cancer has a way of evading treatment. Tumors that were held in check begin to spread anew, forcing doctors to try different drugs in a desperate race to keep malignant cells from multiplying. For a common type of breast cancer, this usually happens because of changes in a gene called ESR1. Mutations there can drive cancer growth even as physicians' first choice of therapy chokes off the resources that tumors had relied on to survive. Afterwards, the prognosis for patients gets worse. Multiple second-line medicines exist, but 'their benefit is limited, quality of life decreases and survival rates are low,' according to Nicholas Turner, director of clinical research and development at the Royal Marsden Hospital in London. New study results from Turner and others show an experimental drug from AstraZeneca, camizestrant, can help sustain the benefit of first-line therapy. Unveiled Sunday, their research found that, once ESR1 mutations are detected, swapping out a standard component of that initial regimen for AstraZeneca's drug reduced the risk of disease progression or death by more than half. Data from the study, which AstraZeneca funded and in February said succeeded, will be presented Sunday afternoon at the American Society of Clinical Oncology's annual meeting. 'Patients have an urgent need for new treatments that can prolong time on first-line therapy and delay disease progression,' Turner said in a statement provided by ASCO. In their clinical trial, Turner and colleagues enrolled 3,256 people with advanced breast cancer positive for hormone receptors but negative for a protein called HER2. These individuals are typically treated with a kind of hormone therapy known as an aromatase inhibitor along with another type of targeted drug that interrupts cancer cell division. Participants in the study were monitored via blood tests for the emergence of ESR1 mutations, which were eventually detected in about 550 people. Three-hundred and fifteen were then randomly assigned to receive camizestrant instead of the aromatase inhibitor or to continue on with their initial regimen. These patients continued to receive those targeted drugs, 'CDK 4/6 inhibitors.' Patients who were switched to camizestrant had a 56% lower risk of their cancer progressing or killing them than those who continued on, researchers calculated. Put another way, people in the camizestrant group lived a median of 16 months without disease progression or death, compared to 9.2 months for those in the control arm. Data also showed camizestrant helped maintain quality of life for longer than did aromatase inhibitors, too. Researchers continue to follow study participants to measure differences between the groups in overall survival, but don't yet have enough follow-up data to determine whether there is a benefit on that score. Less than 2% of patients in either group discontinued treatment due to side effects, which, for camizestrant, were consistent with what AstraZeneca has observed in prior testing. Hormone receptor-positive, HER2-negative tumors are the most common type of breast cancer, accounting for an estimated 70% of cases. Hormone receptors provide a dock for estrogen, which spurs the tumor to grow. In first-line therapy, hormone therapy shuts off estrogen signaling by either gumming up hormone receptors on the surface of breast cancer cells, or by blocking the body from making estrogen. But about 40% of patients whose breast cancer is responsive to hormone therapy develop ESR1 mutations during their initial therapy, according to an estimate cited by ASCO. Research done a decade ago at Memorial Sloan Kettering Cancer Center discovered that ESR1 mutations change the shape of the estrogen receptor, essentially flipping it 'on,' whether or not cancer cells continue to receive an estrogen growth signal. Camizestrant offers a way to get ahead of that change by breaking down the estrogen receptor entirely. It's one of a new crop of so-called selective estrogen receptor degraders, or SERDs, that are taken orally rather than injected like the drug fulvestrant, which has been a staple of breast cancer treatment for decades. One member of this fresh class, Orserdu, won U.S. approval in 2023. Others from Eli Lilly and Roche, as well as a different kind of degrader from partners Pfizer and Arvinas, are in late-stage testing. Data from a Phase 3 trial involving Pfizer and Arvinas' vepdegestrant in people whose hormone receptor-positive, HER2-negative breast cancer progressed following initial treatment were presented at ASCO Saturday. The setting envisioned by camizestrant's trial is one step earlier, subbing in a SERD before initial disease progression to allow patients to remain on first-line therapy longer. 'When patients progress on scans, we're already behind. We've already lost control, in some sense,' Eleonora Teplinsky, head of breast and gynecologic medical oncology at New Jersey's Valley-Mount Sinai Comprehensive Cancer Care, said in a press conference held by ASCO. 'An early switch approach, before we see disease progression on imaging, [allows] us to stay ahead of the curve.' Switching early requires regular monitoring, which Turner and his colleagues accomplished by using 'liquid biopsies,' tests that pick up fragments of tumor DNA circulating in the blood. While these are relatively expensive, Turner said he hopes insurance would cover them should camizestrant win approval in the tested setting. Clearance would also change doctors' testing practice. Soon after Orserdu won U.S. approval, ASCO updated its treatment guidelines to recommend testing for ESR1 mutations following disease progression or recurrence. Camizestrant's benefit lies in delaying that progression, making active surveillance beforehand essential. 'The difference here is this serial monitoring for evidence of the evolving mutation,' said Julie Gralow, an oncologist and ASCO's chief medical officer, at the press conference. Establishing reimbursement and updating guidelines will be important to that goal, acknowledged Mohit Manrao, a senior vice president in AstraZeneca's U.S. oncology division. 'The good part here is that the test exists,' he added 'It is already being done at the point of progression,' he said. AstraZeneca plans to use the data presented at ASCO to request regulatory approval. It is also studying replacing aromatase inhibitors with camizestrant upfront, rather than waiting for ESR1 mutations to emerge. Two other trials are examining camizestrant's potential in early breast cancer.
Daily Mail
01-06-2025
- Business
- Daily Mail
Major discovery about 'invisible' breast tumours that are too small to show up on scans
Thousands of women have been thrown a lifeline thanks to a 'next generation' drug that can destroy breast cancer tumours, months before they even grow. The daily pill, known as camizestrant, stops cancer cells from developing, slowing the spread of the disease and delaying the need for gruelling chemotherapy. Around seven in ten breast cancer patients in the UK have a type of the disease known as HR positive HER-2 negative breast cancer—the most common form. Of these, around 40 per cent can develop an aggressive genetic mutation that makes their outlook incredibly bleak. But the 'transformational' trial found patients given the drug camizestrant saw their risk of the cancer progressing slashed by more than half. It was also the first worldwide study that showed blood tests, rather than scans, can pick up early signs of cancer returning. Doctors first used the test, known as a liquid biopsy, to spot changes in the cancer's DNA—when they found signs of an ESR1 mutation, some patients were given camizestrant, while others stayed on their usual treatment. Experts presenting the findings today at the American Society for Clinical Oncology conference (ASCO) in Chicago, hailed it a 'pivotal moment in breast cancer care' and 'truly fundamental shift in how we approach cancer'. The drug is already being fast-tracked for use in the US and has been sent for approval in the UK. Professor Nicholas Turner, an expert in molecular oncology at The Institute of Cancer Research, London and the Royal Marsden NHS Foundation Trust, who co-led the major trial, said: 'This is a pivotal moment in breast cancer care. 'This proactive approach also redefines how we think about drug resistance in this type of breast cancer. 'This is a potential new treatment strategy in oncology to treat developing resistance before it causes disease progression.' Professor Kristian Helin, chief executive of The Institute of Cancer Research, London, added: 'The results represent more than a clinical milestone—they represent a transformational shift in how we approach precision medicine. 'It is very exciting to see this technology being used to delay disease progression in patients and extend the benefits of treatment in patients with this type of advanced breast cancer and delay the need for chemotherapy for as long as possible. 'These breakthroughs are helping shape personalised breast cancer treatment, allowing doctors to adjust therapies earlier and improve patient outcomes.' In the trial, 3,325 patients HR positive HER-2 negative advanced breast cancer from 23 countries were screened for ESR1 mutations using a liquid biopsy every eight to 12 weeks. Of these, 315 women who tested positive for an ESR1 mutation were given either AstraZeneca's camizestrant and a medicine known as a CDK4/6 inhibitor or another hormone therapy as well as a CDK4/6 inhibitor. Researchers found those on the camizestrant combination slashed their risk of death or the cancer progressing by 56 per cent. The drug also kept the cancer at bay for 16 months on average compared to 9.2 months on standard treatment. Just one per cent of patients stopped taking the drug over side effects. Presenting the findings at ASCO, Susan Galbraith, executive vice president of oncology at AstraZeneca said the drug had now been given 'breakthrough therapy designation' by the Food and Drugs Administration in the US, helping to speed up regulatory review. 'We are having ongoing discussions with regulatory authorities including the UK', added. Dave Fredickson, AstraZeneca's executive vice president of oncology business unit, also said the drug demonstrated a 'truly fundamental shift in how we approach cancer care. 'We're moving away from a one size fits all era and targeting cancer early.' Meanwhile, Dr Catherine Elliott, director of research at Cancer Research UK, said: 'This study is a clear example of how blood tests are starting to transform cancer treatment. 'By tracking tiny traces of tumour DNA in the blood, researchers were able to spot early signs of treatment resistance and switch therapies before cancer had a chance to grow. 'It shows how circulating tumour DNA—or ctDNA—could help doctors make smarter, more timely treatment decisions. 'This approach could become an important part of how we personalise care for people with advanced breast cancer.'
