CDSCO Flags MSD Pharma’s Cancer Drug Trial Over Indian Representation, Control Arm

New Delhi: The Subject Expert Committee (SEC) on Oncology under the Central Drugs Standard Control Organization (CDSCO) has raised critical concerns over the Phase III clinical trial proposal of Sacituzumab Tirumotecan submitted by MSD Pharmaceuticals Pvt. Ltd., directing the company to provide detailed justifications regarding its study design and patient representation in India.

MSD Pharmaceuticals Pvt. Ltd., the Indian subsidiary of global biopharmaceutical company Merck & Co., presented its Phase III clinical trial Protocol No. MK2870-032, Version 00, dated February 18, 2025, for evaluation.

Sacituzumab Tirumotecan is an investigational antibody-drug conjugate (ADC) being developed for the treatment of various cancers, including triple-negative breast cancer and metastatic urothelial carcinoma. The drug combines a humanized monoclonal antibody targeting the Trop-2 receptor with a cytotoxic topoisomerase I inhibitor payload, enabling selective delivery of chemotherapy directly to tumor cells while minimizing systemic toxicity.

During the SEC review, the committee identified two significant issues. Firstly, the proposed control arm in the study was not aligned with the current standard of care, prompting the SEC to ask the company for a clear scientific rationale behind its selection. Secondly, the committee noted that the proposed inclusion of only 60 Indian patients – representing less than 3% of the global trial population of 2,400—was inadequate to generate statistically meaningful outcomes for the Indian population.

The SEC emphasized that such limited representation could compromise the reliability and applicability of trial results in India, potentially affecting regulatory evaluation and future patient access. In light of this, the committee requested MSD Pharmaceuticals to substantially increase the Indian sample size to ensure appropriate representation and robust statistical validity.

After detailed deliberation, the SEC directed the company to submit comprehensive justifications regarding the control arm choice and provide a revised study plan with an expanded Indian cohort. The committee clarified that the trial cannot proceed for further consideration until these issues are adequately addressed, reinforcing the importance of robust trial design and sufficient patient representation for global oncology studies conducted in India.

Also Read: MSN Lab gets CDSCO panel nod for Phase IV CT of Tofacitinib Oral Solution

Powered by WPeMatico

Pharmacist Suspended, New Dispensing Guidelines Issued in Rajasthan Amid Cough Syrup Row

Jaipur: The cough syrup controversy in Rajasthan has now led to suspensions and sweeping new guidelines, as the health department cracked down on lapses following the deaths of children allegedly linked to dextromethorphan hydrobromide syrup. The state government suspended a pharmacist and a doctor of Hathideh PHC in Ajitgarh block, Sikar, for allegedly prescribing the syrup to a child, despite the drug not being recommended for children under four.

According to a recent media report in the Times of India, Director of Public Health Dr Ravi Prakash Sharma confirmed the disciplinary action and announced fresh directives for medical staff. The guidelines stress that no medicine can be dispensed without a valid prescription, and doctors must refrain from prescribing dextromethorphan syrups to children. Patients too have been warned against self-medication, with officials highlighting that unregulated use of the syrup can be dangerous.

Also Read: Probe Launched Against Rajasthan Pharma Firm Over Dextromethorphan Syrup-Linked Death

The controversy escalated after multiple cases were reported across Rajasthan. While fatalities in Sikar and Bharatpur drew attention, the health department clarified that not all cases resulted in death. In one instance, three-year-old Gagan, son of Monu Joshi from Bharatpur, developed cough and fever and was given the syrup by his father without prescription. He later fell ill but recovered after hospital treatment and was discharged, underscoring the risks of unsupervised use, reports Times of India

Also Read: Odisha: Huge cache of banned cough syrups seized, 3 arrested

Powered by WPeMatico

Orthopaedic Surgeon accused of exploiting woman over marriage promise

Thane: An orthopaedic surgeon from Ambernath has been accused of sexual exploitation by a woman. The woman, whose husband was earlier treated by the doctor, alleged that he took advantage of her following her husband’s death. 

Alleging the doctor sexually assaulted her under the pretext of marriage, the widow filed a complaint against the doctor, and accordingly, he is booked under relevant sections of BNS. 

Also read- Doctor gets bail in alleged sexual assault of 17-year-old boy

According to the complainant, the doctor approached her and promised to marry her. She claimed that he believed him and therefore entered into a relationship with him. They had repeated sexual interactions, as per the TOI media report. 

The situation took a turn when the complainant alleged that she realised that the doctor had deceived her. Following this, she approached the police and filed a complaint against the doctor. 

Based on her statement, the police registered an FIR, and further investigation is underway.

Medical Dialogues recently reported that a gynaecologist posted at the sub-district hospital in Banihal, Jammu and Kashmir’s Ramban district, was arrested by the police following allegations of misconduct involving a female patient. The incident took place when a female patient levelled allegations of misconduct against a consultant gynaecologist at the sub-district hospital, Banihal, triggering anger among people in the area. 

Also read- Banihal Gynaecologist suspended over alleged misconduct with patient

Powered by WPeMatico

DoP Notifies Rs 5000 Cr PRIP Scheme to Boost Pharma, MedTech R&D

New Delhi: The Department of Pharmaceuticals (DoP) has notified major amendments to the Scheme for Promotion of Research and Innovation in Pharma MedTech Sector (PRIP) through a recent Gazette notification, with a massive financial outlay of Rs 5000 crore from FY 2023-24 to FY 2029-30.

The scheme aims to transform India’s pharma and MedTech sector from cost-driven to innovation-led growth, build robust research infrastructure, foster global collaborations, and accelerate commercialization of indigenous technologies.

The scheme operates through two components.

Under Component A, seven Centres of Excellence (CoEs) will be set up at NIPERs in Mohali, Ahmedabad, Hyderabad, Guwahati, Kolkata, Hajipur, and Raebareli, with a budget of ₹700 crore. Each CoE will specialize in priority areas such as anti-viral/anti-bacterial drug discovery, medical devices, bulk drugs, flow chemistry, novel drug delivery systems, phytopharmaceuticals, and biological therapeutics.

Component B provides direct financial assistance to startups, MSMEs and industry for both early-stage and late-stage R&D projects. Early-stage projects can receive up to ₹5 crore (without co-funding if the project cost ≤₹1 crore), while late-stage projects may avail up to ₹100 crore with a cap of 35% central funding. For Strategic Priority Innovations addressing critical public health issues like orphan drugs or antimicrobial resistance, assistance may extend up to 50%. The notification details strong emphasis on industry–academia collaboration, encouraging joint projects with reputed government research institutions. Nine slots each are reserved for early and late-stage projects undertaken in partnership with such institutions.

The scheme also promotes intellectual property licensing, incubation, mentorship, and partnerships across startups, investors, academia, NGOs, and government bodies through dedicated online platforms. Funding disbursement will be milestone-linked, with mandatory financial closure proofs and co-funding where applicable.

Also Read: DoP invites applications for research, innovation projects under PRIP scheme

Beneficiaries will also be bound by structured profit-sharing mechanisms, offering options of fixed-rate payments, graded royalty, or equity dilution in proportion to government support, ensuring accountability and reinvestment in public research. Identifying six priority R&D domains, the scheme covers new drugs (including NCEs, biologics, precision medicines, and phytopharmaceuticals), complex generics, biosimilars, cell and gene therapies, high-value patented/near-expiry drugs, and advanced medical devices such as robotic surgical tools, AI/ML-based diagnostics, telemedicine equipment, and biomarker-driven precision devices.

With a ₹4200 crore allocation under Component B alone, the scheme positions India to raise its share in the global pharma market from the present 3.4% to 5% by 2030, translating into a $160 billion industry.

Officials stressed that the reforms align with the ‘One Health’ vision, with spillover benefits for both human and animal health sectors.

Senior Economic Adviser Awadhesh Kumar Choudhary noted that the initiative represents “a decisive step to build a self-reliant and globally competitive Pharma-MedTech ecosystem blending public investment, academic excellence, and private innovation.”

To view the official Gazette, click on the link below:

https://medicaldialogues.in/pdf_upload/gazette-notification-dated-011020250-303178.pdf
Also Read: DoP promotes RnD in Pharma Medtech Sector with AI Integration

Powered by WPeMatico

GLP-1RAs Show Promise for Kidney Protection in Type 2 Diabetes, Reveals Research

Italy: A new review published in Minerva Medica has revealed that GLP-1 receptor agonists may help preserve kidney function in people with type 2 diabetes.

Researchers led by Alessandro Perencin from the Department of Medicine (DIMED), Geriatrics Division, University of Padua, Italy, conducted a systematic review to examine whether this class of diabetes medications could provide direct kidney benefits. GLP-1 receptor agonists (GLP-1RAs) are already widely prescribed for blood sugar management and cardiovascular protection, but their potential to safeguard kidney health has not been comprehensively evaluated until now.
To assess this possibility, the team performed an extensive search of medical literature across databases such as PubMed, Embase, Web of Science, and the Cochrane Library. They looked for studies that reported kidney-related outcomes—specifically estimated glomerular filtration rate (eGFR), a key measure of kidney function, and albumin-to-creatinine ratio (ACR), an indicator of protein leakage in the urine—in adults with type 2 diabetes who were treated with GLP-1RAs. Each study was carefully reviewed for quality and risk of bias to ensure reliable conclusions.
Thirteen studies, including both randomized clinical trials and observational analyses, met the inclusion criteria. These investigations suggest that GLP-1RAs may slow the progression of kidney damage, reduce proteinuria, and improve other important markers of renal health in patients with diabetes. Several studies showed significant slowing of eGFR decline and reductions in ACR, pointing to a possible protective effect against diabetic kidney disease.
However, the evidence was not entirely consistent. While some studies demonstrated clear and measurable benefits, others reported only modest improvements or no significant impact on kidney function. Differences in study design, patient populations, and treatment duration may partly explain these mixed results.
Despite these variations, the authors underscore that the overall trend is encouraging. With diabetic kidney disease remaining a major cause of chronic kidney failure worldwide, therapies that can both control blood glucose and support kidney health are urgently needed. GLP-1RAs—already known to lower cardiovascular risk—could offer an added advantage by helping to preserve renal function over time.
The review calls for larger, well-structured clinical trials to confirm these preliminary findings and to clarify how GLP-1RAs exert potential nephroprotective effects. Establishing clear evidence could help physicians decide when and how to incorporate these drugs into treatment plans for people with type 2 diabetes who are at risk of kidney complications.
“The systematic review highlights the emerging role of GLP-1 receptor agonists as more than just blood sugar–lowering agents. While further research is necessary, these medications may one day become a cornerstone not only in managing type 2 diabetes and cardiovascular disease but also in protecting long-term kidney health,” the authors concluded.
Reference:
Perencin A, Ceolin C, Papa MV, Di Marzio B, Zanforlini BM, Devita M, et al. Glucagon-like peptide-1 receptor agonists and its possible nephroprotective role: a systematic review. Minerva Med 2025 Sep 11. DOI: 10.23736/S0026-4806.25.09709-5

Powered by WPeMatico

GLP-1 Receptor Agonists Show Gastrointestinal Safety with Some Risks: Study

USA: Researchers have found in a retrospective study that GLP-1 receptor agonists (RAs) are generally safe for the gastrointestinal (GI) and hepatobiliary systems in patients with type 2 diabetes (T2D).    

The study published in the American Journal of Gastroenterology revealed that the therapy was linked to lower risks of several GI cancers and complications compared with other oral antidiabetic drugs. However, GLP-1 RAs were associated with a higher risk of gastroparesis and intussusception, highlighting the need for careful monitoring in vulnerable patients.
The study, led by Dr. Chengu Niu from the Department of Internal Medicine, Rochester General Hospital, USA, analyzed electronic health records of adults with T2D treated across the United States between 2010 and 2020. Using data from the TriNetX network, researchers conducted a retrospective cohort analysis and included 230,415 patients receiving GLP-1 RAs, matched 1:1 with an equal number of patients on other oral antidiabetic medications such as metformin, empagliflozin, and sitagliptin.
Over a five-year follow-up, the study evaluated various GI and hepatobiliary outcomes, including gastroparesis, bowel obstruction, pancreatitis, cholecystitis, and related GI cancers.
The analysis revealed the following findings:
  • GLP-1 RA use was associated with a higher risk of gastroparesis (HR 1.591).
  • GLP-1 RA use was associated with a higher risk of intussusception (HR 1.383).
  • GLP-1 RA therapy was linked to 15%–26% lower risks of cholangitis, bowel obstruction, ileus, volvulus, chronic pancreatitis, and procedures such as endoscopic retrograde cholangiopancreatography compared to other oral antidiabetic drugs.
  • GLP-1 RA users had lower risks of pancreatic cancer (HR 0.897), gastric cancer (HR 0.838), esophageal cancer (HR 0.741), and colorectal cancer (HR 0.870).
  • There were no significant differences in the risk of biliary cancer or hepatocellular carcinoma between GLP-1 RA users and other oral antidiabetic drug users.
  • Rates of acute pancreatitis, cholecystitis, and cholecystectomy were similar between GLP-1 RA users and the control group.
  • Overall, these findings support the gastrointestinal and hepatobiliary safety of GLP-1 receptor agonists.
The findings suggest that for patients at risk of common GI malignancies or conditions such as cholangitis and bowel obstruction, GLP-1 RAs remain a viable and generally safe option. However, clinicians are advised to exercise caution in patients with preexisting gastroparesis or intussusception, who may benefit from traditional oral antidiabetic therapies instead.
The authors noted several limitations of the study. The results show associations rather than causation, and the five-year follow-up period may not fully capture long-term cancer risks. Socioeconomic factors, access to healthcare, treatment adherence, and medication switching were not assessed and could have influenced outcomes.
“The large real-world analysis supports the gastrointestinal and hepatobiliary safety of GLP-1 receptor agonists in patients with type 2 diabetes, while highlighting the need for vigilance regarding specific complications such as gastroparesis and intussusception. Further long-term studies are needed to confirm these findings and to better assess potential cancer risks associated with GLP-1 RA therapy,” the authors concluded.
Reference:
Niu, Chengu MD1,a; Sun, Kefang MD1; Zhang, Jing MD2; Elkhapery, Ahmed MD1; Zhu, Kaiwen MD1; Malik, Sheza MD1; Xue, Chao MD1; Okolo, Patrick I MD3. Gastrointestinal and Hepatobiliary Safety of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes. The American Journal of Gastroenterology ():10.14309/ajg.0000000000003760, September 03, 2025. | DOI: 10.14309/ajg.0000000000003760

Powered by WPeMatico

Continuing ACE Inhibitors and ARBs Before Non-Cardiac Surgery Linked to Lower Postoperative Mortality and Functional Decline: Study

Continuing angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers before non-cardiac surgery is linked to a reduced risk of postoperative mortality and functional decline, according to researchers from Science Tokyo. Using a Japanese nationwide registry of 2.6 million patients over 50 years old, the researchers compared outcomes between those who continued antihypertensive therapy and those who did not. Their findings highlight potential benefits of specific classes of antihypertensive drugs depending on type of surgery needed.

Hypertension, or high blood pressure, affects nearly 1.3 billion people globally and is a leading risk factor for serious health issues. When patients with this condition need to undergo surgery, doctors must decide on how to handle their daily blood pressure medication. This is a critical choice, given that the wrong call can lead to severe complications and a decline in the patient’s physical function after the operation.

Unfortunately, this challenge is made even more difficult due to an ongoing debate in the medical community about two main classes of antihypertensive drugs: angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Some doctors hold that continuing these medications can lead to a dangerous drop in blood pressure during surgery. Others have argued that stopping them may instead trigger a dangerous spike in blood pressure, which can damage multiple organs. This lack of consensus creates a clinical dilemma for doctors and puts patients at risk.

In a recent study, a research team led by Associate Professor Shintaro Mandai along with second year MD-PhD student Rena Suzukawa and Professor Shinichi Uchida from the Department of Nephrology at the Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (Science Tokyo), Japan, sought to settle this issue. The study was conducted in collaboration with Professor Kiyohide Fushimi from the Department of Health Policy and Informatics, Science Tokyo. Their paper, which was published in Volume 5, Issue 4 of the European Heart Journal Open on August 11, 2025, explored the association between six classes of antihypertensive drugs and postoperative outcomes in patients undergoing non-cardiac surgeries.

Using a large nationwide registry of patient claims in Japan, the team analyzed data from approximately 2.6 million patients aged 50 years or older. They compared outcomes between patients who continued their antihypertensive therapy before and after surgery and those who did not. They also analyzed the outcomes for different combinations of drugs and whether the type of surgery was a meaningful factor.

Through comprehensive statistical analyses, the researchers revealed that patients who continued taking ACEis or ARBs had a significantly lower risk of mortality and functional decline after non-cardiac surgeries. Interestingly, these benefits were most evident among patients who underwent orthopedic or gastrointestinal surgeries, where they were also associated with a lower risk of sepsis.

These results have important clinical implications as Mandai explains, “By demonstrating the benefits of ACEis and ARBs in an area where randomized controlled trials are difficult to conduct, this study suggests the potential for preventing postoperative complications and maintaining quality of life in older adults.” The general findings contribute to ongoing discussions about perioperative antihypertensive management and suggest that continuing ACE inhibitors and ARBs, rather than withholding them as some clinicians advocate, may be linked to better postoperative outcomes.

Moreover, the study underscores a broader point about the untapped potential of common medications. “Although essential medications such as antihypertensive drugs are often discussed in the context of negative aspects like polypharmacy, this work hints at their added clinical value,” says Mandai. By focusing on these beneficial off-target effects, this research provides a new perspective on inpatient care.

Overall, these efforts by Mandai and his team will hopefully pave the way for practical guidelines for doctors managing patients with hypertension, helping them improve surgical outcomes worldwide.

Reference:

Rena Suzukawa, Shintaro Mandai, Yuta Nakano, Shunsuke Inaba, Hisazumi Matsuki, Yutaro Mori, Fumiaki Ando, Takayasu Mori, Koichiro Susa, Soichiro Iimori, Shotaro Naito, Eisei Sohara, Tatemitsu Rai, Kiyohide Fushimi, Shinichi Uchida, Perioperative antihypertensive medications and effects on functional decline and mortality in non-cardiac surgery, European Heart Journal Open, Volume 5, Issue 4, July 2025, oeaf096, https://doi.org/10.1093/ehjopen/oeaf096

Powered by WPeMatico

Sequential Herbal Irrigation Safe and Biocompatible Alternative in Pediatric Endodontics: Study

A randomized controlled trial published in the Journal of Indian Society of Pedodontics and Preventive Dentistry (July–September 2025 issue) by Shrikant Bhujangrao Kendre, Anuja U. Bhatane, Mahesh Vilasrao Dadpe, Yogesh Jagannath Kale, and Prasanna Trambakrao Dahake has reported that sequential herbal irrigation may offer a safe and effective alternative to conventional irrigants in the endodontic treatment of primary teeth.

The authors point out that while sodium hypochlorite, ethylenediaminetetraacetic acid, and chlorhexidine are commonly used to disinfect root canals, they can pose risks such as cytotoxicity, unpleasant taste, and tissue irritation—factors of particular concern in young children. The study found that a herbal protocol combining Salvadora persica (Miswak), Azadirachta indica (Neem), tea tree oil, and phytic acid achieved antimicrobial efficacy comparable to chemical irrigants, with the added advantages of biocompatibility and safety.

The trial involved 15 children aged 4 to 8 years with bilateral primary molars indicated for pulpectomy, making it one of the first controlled comparisons of sequential herbal and conventional irrigants in pediatric patients. Both treatment groups showed significant microbial reduction, but herbal irrigation demonstrated slightly greater activity against Enterococcus faecalis, a key bacterium implicated in endodontic failure.

Although the difference in efficacy against Prevotella intermedia was not statistically significant, the overall results underscored that the herbal regimen could match or even surpass chemical alternatives in effectiveness. By integrating multiple plant-based agents with known antimicrobial and chelating properties, the sequential protocol leveraged the synergistic action of natural compounds to disinfect root canals while minimizing potential adverse effects.

According to the authors, the findings highlight the promise of herbal irrigants in pediatric dentistry, where tolerance, safety, and biological compatibility are as important as antimicrobial efficacy. The ability to achieve reliable bacterial reduction without exposing children to harsh chemicals makes sequential herbal irrigation a potential game changer in clinical practice. The researchers recommend further trials on larger patient populations to confirm these outcomes and to standardize protocols for herbal use. Still, the study marks an important step in advancing natural, biocompatible strategies in pediatric endodontics.

Reference:

Kendre SB, Bhatane AU, Dadpe MV, Kale YJ, Dahake PT. Comparative evaluation of antibacterial efficacy of sequential herbal irrigation with conventional irrigation in endodontic therapy of primary teeth: A randomized controlled trial. J Indian Soc Pedod Prev Dent. 2025;43(3):410–417. doi:10.4103/jisppd.jisppd_253_25

Powered by WPeMatico

Sarcoidosis Patients at Higher Risk of Psychiatric Symptoms, Meta-Analysis Finds

Belgium: Patients living with sarcoidosis appear to be at a markedly higher risk of developing psychiatric symptoms compared to healthy adults, a new systematic review and meta-analysis published in Frontiers in Medicine has revealed.

The study by Andreas Frans and colleagues from the Department of Medical Psychology and Psychiatry, Antwerp University Hospital, Belgium, highlights the need for routine psychiatric screening in sarcoidosis care to improve patient outcomes. 

Sarcoidosis, a multisystem inflammatory disorder, has long been recognized for its impact on physical health, but its association with psychiatric symptoms and syndromes (PSS) has remained underexplored. To address this gap, the researchers conducted a comprehensive review of existing literature, analyzing 43 studies and 53 case reports that examined psychiatric manifestations in sarcoidosis patients. The meta-analysis included data from 962 patients and assessed the prevalence and risk of psychiatric symptoms compared to healthy controls.
The study revealed the following findings:
  • Fatigue was reported in 54% of sarcoidosis patients.
  • Excessive daytime sleepiness affected approximately 50% of patients.
  • Depression was observed in 25% of patients.
  • Anxiety was reported in 29% of patients.
  • Sleep disturbances and insomnia were present in 27% of cases.
  • Neurocognitive symptoms were reported in 29% of patients.
  • Fatigue and depressive symptoms had the strongest associations with sarcoidosis (OR 20.2 and 4.8, respectively).
  • Overall, sarcoidosis patients have a fivefold higher risk of psychiatric symptoms compared to healthy adults.
The study highlights that psychiatric symptoms in sarcoidosis are multifaceted, ranging from mood and anxiety disorders to cognitive impairments and severe manifestations such as psychosis or catatonia, as noted in individual case reports. The interplay between chronic inflammation, the disease itself, and potential side effects of sarcoidosis treatments may contribute to the development of PSS, emphasizing the complex etiopathogenesis.
Given these findings, the authors advocate for the systematic use of standardized psychiatric assessment tools in routine sarcoidosis management. Early identification and intervention for psychiatric symptoms could help mitigate their impact on quality of life and overall disease outcomes. They also call for future research to focus on larger, multicenter studies, interventional trials, and interdisciplinary care models to better understand and treat psychiatric comorbidities in this population.
“This meta-analysis confirms that sarcoidosis is not only a physical health burden but also significantly affects mental health,” the researchers noted. “Integrating psychiatric evaluation into routine clinical care is crucial for improving patient well-being and treatment outcomes.”
“The study reinforces the need for heightened awareness of psychiatric complications in sarcoidosis. Addressing these challenges through early screening, multidisciplinary care, and targeted interventions can help optimize management and enhance the quality of life for patients living with this complex disease,” they concluded.
Reference:
Frans, A., Van Hoye, G., Van Meerbeeck, X., & Morrens, M. (2025). Psychiatric symptoms and syndromes in sarcoidosis: A systematic review and meta-analysis. Frontiers in Medicine, 12, 1634175. https://doi.org/10.3389/fmed.2025.1634175

Powered by WPeMatico

Adjuvant Radiotherapy or ET Lowers Locoregional Recurrence Rates Risk in Early-Stage Breast Cancer: JAMA

USA: Researchers have found in a new study that adjuvant radiotherapy (RT) or endocrine therapy (ET) significantly reduces the risk of locoregional recurrence (LRR) in patients with early-stage breast cancer and low genomic risk.

The findings, published in JAMA Network Open by David Gibbes Miller from the Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, and colleagues, highlight the importance of treatment adherence and suggest the potential role of genomic biomarkers in guiding de-escalation strategies.
The study addressed a critical question in breast cancer management: whether omission of RT or ET is associated with higher rates of recurrence among women with favorable tumor biology. Although treatment de-escalation is often considered for older women with early-stage breast cancer, limited evidence exists on whether younger patients could also safely undergo less intensive treatment with guidance from biomarker testing, such as the Oncotype DX 21-gene recurrence score (ODX RS).
The researchers examined outcomes for 2249 women aged 50 to 69 years, all of whom had hormone receptor–positive, ERBB2-negative, stage T1N0 breast cancer with an ODX RS of 18 or below. All patients underwent lumpectomy between January 2007 and January 2023. Among them, 92.3 percent also received RT alongside ET. Patients were classified based on adherence to ET, defined as taking ET for at least five years or continuing treatment at the last follow-up. The median follow-up period was 63.3 months, allowing long-term assessment of outcomes.
The key findings of the study were as follows:
  • The 72-month cumulative incidence of locoregional recurrence (LRR) was 8.0% in patients who did not receive radiotherapy (RT), compared with 1.1% in those who underwent RT, showing a significant difference.
  • Patients receiving RT had the lowest recurrence risk regardless of endocrine therapy (ET) adherence.
  • The combination of RT and adherence to ET resulted in a 72-month LRR of 1.1%.
  • RT with ET nonadherence showed a similar 72-month LRR of 0.9%.
  • ET alone, when adhered to but without RT, was linked to a higher 72-month LRR of 5.5%.
  • The highest recurrence rate, 11%, occurred in patients who received neither RT nor adhered to ET.
An important observation was that receipt of RT did not significantly impact overall survival, suggesting that its main benefit lies in local disease control rather than extending lifespan. Still, the analysis clearly indicates that adherence to at least one adjuvant modality remains vital in reducing recurrence among patients even when they have low genomic risk.
The authors note that while the absolute recurrence risk remains low for this group, the relative reduction achieved through adjuvant therapy is meaningful. They argue that the ODX RS may serve as a valuable tool in determining which younger patients might accept modestly higher recurrence risks in exchange for reduced therapy burden. However, they caution that each treatment approach carries its own risks and adverse effects, making shared decision-making between clinicians and patients essential.
“The cohort study demonstrates that both radiotherapy and endocrine therapy significantly lower the chances of locoregional recurrence in women with early-stage, low genomic risk breast cancer. For patients unwilling to receive both therapies, adherence to at least one still provides substantial benefit, reinforcing the importance of individualized treatment plans based on genomic testing and patient preferences,” the authors concluded.
Reference:
Miller DG, Boe LA, Wen HY, et al. Adjuvant Radiation and Endocrine Therapy in Early-Stage Breast Cancer With Low Genomic Risk. JAMA Netw Open. 2025;8(9):e2532305. doi:10.1001/jamanetworkopen.2025.32305

Powered by WPeMatico