Combination therapy improves outcomes for advanced triple-negative breast cancer: Study

 A new study led by researchers at the Icahn School of Medicine at Mount Sinai has found that adding the targeted therapy everolimus to standard carboplatin chemotherapy extends the time before disease progression in patients with advanced triple-negative breast cancer (TNBC), one of the most aggressive and hard-to-treat forms of breast cancer.

The randomized phase 2 clinical trial, published in Breast Cancer Research and Treatment, showed that patients receiving the combination treatment experienced a 52 percent reduction in the risk of disease progression or death compared to those treated with carboplatin alone. The regimen was well tolerated, with no unexpected safety concerns.

“Triple-negative breast cancer has limited treatment options and is often resistant to standard therapies,” said senior author Amy Tiersten, MD, Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine. “Our findings suggest that the combination of carboplatin and everolimus could offer a new option for patients, and should be further tested in larger clinical trials to confirm its effectiveness and safety.”

According to the American Cancer Society, triple-negative breast cancer is a type of breast cancer that makes up about 10 to 15 out of every 100 cases. It’s tougher to treat and can be more dangerous than other kinds of breast cancer.

Many TNBC tumors are missing something called the PTEN gene, which usually helps keep cell growth under control. Without PTEN, a “growth switch” called the mTOR pathway gets turned on, making the cancer grow faster. Everolimus can block this switch, which may slow down or even stop the cancer from spreading.

In this study, Mount Sinai doctors worked with patients whose TNBC had already been treated up to three times before. They randomly chose some patients to receive carboplatin (a common chemotherapy) alone, while others got carboplatin plus everolimus. The patients who got both medicines lived without their cancer getting worse for longer than those who got only chemotherapy. “This combination could represent a promising new treatment option for advanced triple-negative breast cancer if validated in phase 3 trials,” said Rima Patel, MD, Assistant Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine and first author of the study.

Future phase 3 studies will be needed to confirm the efficacy of carboplatin and everolimus in metastatic TNBC. If the efficacy of the combination is confirmed in larger studies, carboplatin and everolimus could be considered another treatment option for patients with TNBC in lieu of offering carboplatin or another single-agent chemotherapy alone.

Reference:

Patel, R., Fukui, J., Klein, P. et al. Randomized phase II comparison of single-agent carboplatin versus combination of carboplatin and everolimus for advanced triple negative breast cancer. Breast Cancer Res Treat (2025). https://doi.org/10.1007/s10549-025-07802-7

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Osteoarthritis Linked to Increased Risk of Sleep Apnea, Study Finds

Researchers have discovered in a new study that patients with osteoarthritis (OA) are at higher risk of developing sleep apnea (SA), a disease with high morbidity and mortality. Osteoarthritis is the most prevalent joint disease, leading to chronic pain and inflammation, two established risk factors for sleep apnea. The study was published in the journal of Clinical Rheumatology by Yanqiu Zhu and colleagues.

The purpose of the current study was to examine whether OA, such as knee, hip, and hand OA, is linked with a higher risk of sleep apnea. Employing data from the IQVIA Medical Research Database, three individual cohort studies were performed to evaluate the rate of SA among persons with OA versus those without OA.

The research utilized a cohort design of participants who were 50 years and older, stratified into three cohorts according to the type of OA (knee, hip, and hand OA). Each OA patient was matched with a maximum of five non-OA patients according to age, sex, entry-time, and body mass index (BMI) to control for confounding factors.

OA Cohorts:

  • Knee OA: 58,674 patients

  • Hip OA: Not explicitly given in the summary

  • Hand OA: Not specifically provided within the summary

Non-OA Cohorts:

  • Knee OA Comparison Group: 235,850 non-OA participants

The risk incidence of SA was estimated separately within OA and non-OA groups. Cox proportional hazard regression was employed to estimate the association of OA with developing SA, controlled for suspected confounders .

Key Findings

Knee Osteoarthritis

  • SA Incidence: 2.29 per 1,000 person-years for the OA group versus 1.41 per 1,000 person-years for the non-OA group.

  • Risk Increase: Knee OA patients had a 45% increased risk of developing SA (adjusted hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 1.34–1.56).

Hip Osteoarthritis:

  • Risk Increase: Hip OA patients also had a 45% increased risk of SA (adjusted HR: 1.45, 95% CI: 1.28–1.66).

Hand Osteoarthritis:

  • Risk Increase: Hand OA patients had a 50% increased risk of SA (adjusted HR: 1.50, 95% CI: 1.26–1.78).

This study has concluded that patients with knee, hip, and hand osteoarthritis are at significantly increased risk of developing sleep apnea relative to those without OA. These results underscore the need to consider sleep apnea as a possible comorbidity in OA patients and indicate that targeted screening, prevention, and treatment strategies for sleep apnea in OA patients may be an effective way to decrease the overall disease burden.

Reference:

Zhu, Y., Jiang, Q., Zhang, Y. et al. Osteoarthritis and the risk of sleep apnea: a general population-based cohort study. Clin Rheumatol (2025). https://doi.org/10.1007/s10067-025-07457-1

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Bihar Govt approves stipend hike: MBBS, BDS, AYUSH, FMG interns to get Rs 27k per month

Patna: Offering respite to the MBBS, BDS, and AYUSH interns in Bihar, the State Government has announced a stipend hike. Now, the MBBS, BDS, Ayurvedic, Unani, and Homoeopathy Interns in the government medical colleges, Patna Dental College and other institutes across the State will get Rs 27,000 per month. Previously, they used to get Rs 20,000 per month as their stipend.

Apart from this, the State has also announced to give a Rs 27,000 monthly stipend to the Foreign Medical Graduates undergoing mandatory internship in the State’s Government medical colleges.

Meanwhile, the Physiotherapy and Occupational Therapy interns will get Rs 20,000 per month as their stipend, announced the Bihar Government.

Medical Dialogues had earlier reported that the MBBS interns of the State-run Patna Medical College and Hospital (PMCH) were on a protest demanding a hike in their monthly stipend. They had also threatened to intensify their protest by disrupting the out-patient department (OPD) services if their monthly stipend was not increased.

The MBBS interns at PMCH, who were receiving approximately Rs 20,000 as a monthly stipend, were demanding a hike in the stipend amount from Rs 20,000 per month to Rs 40,000 per month.

According to the intern doctors, the State Government had last revised the monthly internship allowance back in 2022, with an assurance to revise it again after three years.

While the MBBS interns across 10 other medical colleges under the Bihar government used to get a monthly stipend of around Rs 19,600, the MBBS interns at IGIMS get Rs 30,000 as a monthly stipend, while those at AIIMS get Rs 32,000.

Meanwhile, the intern doctors in West Bengal and Odisha get Rs 43,000 and Rs 40,000 per month, respectively. Therefore, the interns were urging the State to take immediate action to revise the stipend structure and bring Bihar at par with other States. 

Also Read: Bihar MBBS Interns on Strike Demanding Stipend Hike to Rs 40k

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Supreme Court upholds Telangana’s domicile rule for MBBS admissions

New Delhi: Allowing the appeal of the Telangana Government, the Supreme Court recently upheld the State’s domicile rule that permitted students who have studied for the last four years up to Class 12 in the state, for admissions in medical and dental colleges under the state quota.

In its order, the Apex Court bench comprising Chief Justice B R Gavai and Justice K Vinod Chandran upheld the Telangana Medical and Dental Colleges Admission (Admission into MBBS & BDS Courses) Rules, 2017, which was amended in 2024.

Under this rule, to be eligible for admission to state quota medical and dental seats through the National Eligibility-Entrance Test (NEET), a student must have pursued Classes 9 to 12 in the State.

Earlier, the domicile policy was challenged before the Telangana High Court. Medical Dialogues had earlier reported that more than 50 pleas were filed before the Telangana HC challenging the validity of Rule 3(a) of the Telangana Medical and Dental Colleges Admission (Admission into MBBS & BDS Courses) Rules 2017 as amended vide the GO dated July 19, 2024, which made it mandatory for the MBBS and BDS aspirants to study continuously from Classes 9 to 12 in the State.

While considering the matter, the Telangana HC had held that permanent residents of the State did not need to study in Telangana for 4 continuous years for MBBS and BDS admission in the domicile quota seats. The HC bench had observed that the State’s permanent residents could not be denied benefits of admissions in medical colleges only because they lived outside the State for some time.

However, the HC Division bench of Chief Justice Alok Aradhe and Justice J. Sreenivas Rao had declined to strike down Rule 3(a) of the 2017 Rules, which prescribes the criteria for local candidates, in its entirety.

Also Read: Supreme Court to decide on Telangana domicile quota for MBBS admissions

Back then, the HC bench had reasoned that striking down the provision in its entirety would have the unintended consequence of opening the State quota seats to students from across the country. Instead, the Court had read down the rule to exempt permanent residents of Telangana from the four-year study requirement, while holding that the interpretation in this regard was consistent with Article 371D(2)(b)(ii) of the Constitution, which empowers States to frame special provisions for local candidates in educational institutions.

However, challenging the HC order, the State had approached the top court bench. In its appeal, the Telangana Government argued that the High Court’s expansion of the definition of a “local candidate” undermined the special protection under Article 371D, which was designed to ensure preferential access for students genuinely integrated into the State’s educational system.

On the other hand, the students argued that the definition was unduly rigid and overlooked circumstances such as the transfer of parents in government or allied services, due to which, children get forced to pursue their studies outside of Telangana despite maintaining strong ties to the State.

The top court on August 5 reserved its verdict on the pleas, including one from the Telangana government, against the HC order that struck down its domicile rule for admissions in medical colleges in the state. The state was represented by senior advocate Abhishek Singhvi and lawyer Sravan Kumar Karnam, PTI has reported.

Now, the Apex Court bench comprising Chief Justice of India B.R. Gavai and Justice K. Vinod Chandran allowed the State’s appeal and affirmed the constitutionality of the Telangana Medical and Dental Colleges Admission Rules, 2017 (2017 Rules) as amended in 2024.

“The appeals of the State and the university are allowed, setting aside both the impugned high court judgments. The students’ writ petitions stand dismissed,” observed the bench.

As per the latest media report by The Hindu, while setting aside the High Court bench’s order, the top court bench observed that in the absence of a statutory definition of residence or a prescribed framework for issuing residence certificates, the directions would result in an “anomalous situation”, rendering the domicile unworkable and exposing it to a spate of litigation.

Further, the rule took note of a further amendment proposed by the State Government, adding a proviso to Rule 3 to permit candidates who had studied outside Telangana during the four qualifying years to still be treated as local candidates if they belonged to specified categories, including children of State government employees, All India Services officers, defence personnel, or employees of State corporations and agencies subject to all-India transfers.

“The said proviso should allay and mitigate the grievances of those who claim that they were taken out of the State by compulsion of the movement of their parents outside the State by reason of employment in Government/All-India Services/ Corporations or Public Sector Undertakings constituted as an instrumentality of the State of Telangana as also defence and paramilitary forces who trace their nativity to the State,” observed the Supreme Court.

Further, the Apex Court clarified that the admissions made in the previous academic order, based on a concession extended by the government to mitigate the hardship, would not be disturbed.

Also Read: NEET: SC slams Telangana’s domicile policy, says students who go outside state seeking better education shouldn’t be penalised

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HC strikes down 79% reservation in medical colleges, imposes 50% cap in UP

The Allahabad High Court’s Lucknow bench has quashed Uttar Pradesh government orders that resulted in over 79 percent reservation in government medical colleges in 4 districts.

The direction came on a petition by a NEET 2025 candidate who argued that the state’s orders between 2010–2015 unlawfully pushed reservation beyond the 50% cap, leaving just seven out of 85 seats for the unreserved category. Rejecting the state’s reliance on the Indira Sawhney case, the court ruled that any hike in reservation must follow due legal process. It directed the state to refill seats strictly in line with the UP Reservation Act, 2006, ensuring the 50% ceiling is not crossed.

For more details, check out the full story on the link mentioned below:

HC quashes 79 percent reservation in UP govt medical colleges, orders strict 50 percent cap

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Delhi HC directs private hospital to treat 12-year-old under EWS category

New Delhi: Taking suo motu cognisance of a newspaper report about a 12-year-old boy who was critically injured and was denied admission to government hospitals due to the unavailability of ICU beds, the Delhi High Court directed a private hospital, where the boy was eventually admitted despite his family’s poor financial condition, to provide treatment under the Economically Weaker Section (EWS) category and refrain from demanding any payment from his parents.

A division bench of Justices Prathiba M Singh and Manmeet PS Arora further ordered that Shree Aggrasain International Hospital may make its submissions on the next date of hearing, but, in the meantime, must continue to provide all necessary and adequate treatment for the child’s recovery without charging the parents.

On being informed about the need to broaden the eligibility criteria for the EWS category, since many private hospitals fail to extend mandated facilities despite being under a binding obligation, the bench directed that this issue too shall be taken up on the next date, and counsels for all parties, including the Delhi government, should make their submissions.

Also read- Paramedical staff crucial for health management: Delhi HC directs immediate recruitment

The case concerns a 12-year-old boy who sustained severe injuries after he slipped from the first floor of his house on 19th August, 2025, as reported by TOI on August 29. The boy’s father is a daily wager and faced enormous challenges in finding a ventilator bed at any government hospital in the capital, following which the minor was taken to the Shree Aggrasain International Hospital, Rohini, New Delhi.

The news report also states that the parents of the child were looking for an ICU bed in various hospitals across Delhi, including the Safdarjung Hospital and other Delhi Government hospitals. However, due to their inability to find any ICU bed in any government hospital across the city, the child had to be admitted to a private hospital.

The Bench, which spoke to the child’s uncle over a phone call, was initially considering moving the boy to a government hospital. However, noting the progress in the child’s medical condition, the court decided not to shift him from the current facility.

The court further made it clear till the next date, the hospital will not demand money and continue to treat the child properly.

“The child shall be considered in the EWS category, and no payment shall be demanded by the hospital from the parents of the child till the next date of hearing. Issue notice to the hospital. On the next date, the hospital may make its submissions,” the bench said, posting the matter for September 2. The order would be communicated to the head of the hospital.

Advocate Ashok Agarwal, who was appointed amicus curiae by the court in another case relating to the implementation of the Hospital Management Information System (HMIS), said in the EWS category, the criteria deserve to be increased in the case of hospitals, for most private hospitals did not properly extend medical facilities to the category, though under a binding obligation.

The news report claimed that a few days into his treatment at the government hospital, the child complained of severe headache, nose bleeding and vomiting and was rushed to the private hospital. The report said the family tried to get an admission in Ambedkar Hospital but was turned down twice and was asked to go to hospitals such as G B Pant or Safdarjung.

The child’s father was caught between mounting medical bills and the absence of support in government hospitals. He said he earns a few thousand rupees a month and has already spent Rs 2 lakh on his son’s treatment after borrowing money.

Recently, the Delhi government health secretary informed the high court that once the HMIS was fully implemented, ICU bed availability would begin in real time, reports PTI.

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

Also read- Doctor challenges ‘arbitrary’ revaluation clause in DNB exam- Delhi HC issues notice to NBE, Centre

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Long-Term Metformin Use Linked to Vitamin B12 Deficiency and Neuropathy, Study Finds

USA: A recent study published in Diabetes Research and Clinical Practice highlights a significant concern for individuals with type 2 diabetes mellitus (T2DM) who are on long-term metformin therapy. Researchers, led by Aryana Sepassi from the University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, report that prolonged metformin use is strongly linked to vitamin B12 deficiency and an increased risk of peripheral neuropathy. The findings highlight the importance of routine vitamin B12 monitoring in patients on extended metformin therapy.

The analysis utilized data from the National Institutes of Health’s All of Us research program, providing a large real-world population sample that included 14,808 adults with T2DM. Among these, 61.7% reported metformin use, with nearly 38% classified as long-term users (≥4 years). Researchers employed a retrospective, observational cross-sectional design and compared vitamin B12 status and neuropathy prevalence between long-term users, short-term users (<4 years), and individuals who did not use metformin.
The key findings of the study were as follows:
  • Patients using metformin for four years or more had a 67% higher risk of vitamin B12 deficiency compared with non-users after adjusting for confounding factors.
  • The risk of vitamin B12 deficiency was 38% higher in long-term metformin users compared with those using metformin for a shorter period.
  • The prevalence of peripheral neuropathy was 39% higher among long-term users compared to those on short-term therapy.
  • The difference in neuropathy risk between long-term users and non-users was not statistically significant, but the trend indicated a concerning pattern.
  • The risk of vitamin B12 deficiency increased by approximately 3% for each year following the initiation of metformin therapy, suggesting a cumulative effect over time.
The study highlights a complex interplay between the duration of diabetes, metformin exposure, and neuropathy risk. This relationship emphasizes that neuropathic complications may not solely result from hyperglycemia but also from drug-induced nutritional deficiencies. According to the authors, these findings underscore the necessity of integrating vitamin B12 screening into routine care for patients undergoing prolonged metformin treatment, particularly when they present with symptoms of neuropathy.
The authors acknowledged limitations, including the observational design, which prevents establishing causality, and the inability to fully control for factors such as dietary habits, genetic predispositions, coexisting conditions like anemia, and adherence to vitamin B12 supplementation. Additionally, missing medication history data may have influenced the outcomes.
The researchers conclude that as metformin continues to be widely prescribed—even beyond diabetes care—clinicians should remain vigilant about its long-term implications. Regular vitamin B12 monitoring and timely interventions could be critical in preventing neuropathy, distinguishing its underlying causes, and improving quality of life for patients.
Reference:
Sepassi, A., Wang, J., Yankowski, S., Enkoji, A., Okenwa, M., Morello, C. M., & Hurley-Kim, K. (2025). Associations between long-term metformin use, the risk of vitamin B12 deficiency, and neuropathy: An All of Us research Program study. Diabetes Research and Clinical Practice, 228, 112424. https://doi.org/10.1016/j.diabres.2025.112424

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Treating Heart Failure with Anti-Obesity Medication: Dual Benefits for Clinical Outcomes and Climate Impact

New research has found that the use of GLP-1 receptor agonists*, a class of medications commonly prescribed for patients with obesity and diabetes, reduces the environmental footprint of healthcare and clinical outcomes when used to treat heart failure.

Treatment of heart failure patients with these therapies led to fewer hospitalizations and lower calorie intake, which together translated into decreased greenhouse gas emissions, less medical waste, and reduced water usage.

The study is one of the first to quantify the environmental co-benefits of pharmacologic treatment. The findings are being presented today at the 2025 European Society of Cardiology Congress in Madrid, Spain.

The healthcare sector is responsible for nearly 5% of greenhouse gas emissions globally (1), highlighting the need for interventions to reduce the environmental footprint of clinical care.

Patient level meta-analysis of four randomised controlled trials, SELECT, FLOW, STEP HFpEF, and STEPHFpEF DM, was conducted. All the trials involved patients with a type of heart failure, called heart failure with preserved ejection fraction, who had been treated with GLP-1 receptor agonists or a placebo. Estimates of mean inpatient days, ICU admissions, emergency department and ambulatory visits per event of heart failure, and related greenhouse gas emissions were obtained from previously published literature.

A total of 54 worsening heart failure events were reported among 1,914 patients receiving GLP1-receptor antagonist treatment, compared to 86 events among 1,829 patients receiving placebo.

Those receiving the treatment were estimated to have 9.45 kg CO₂-equivalent emissions per patient per year, compared to 9.70 kg CO₂-equivalent emissions per patient per year among placebo users. The differences were predominantly driven by emissions arising from inpatient stays and outpatient visits due to worsening heart failure events.

The study was led by Dr.Sarju Ganatra, Director of Sustainability and Vice Chair of Research at Lahey Hospital & Medical Center in the US and the President of Sustain Health Solutions, a non-profit organization that helps healthcare organizations integrate sustainability in care delivery. He explained, “The magnitude of the potential environmental emission savings found in our analysis was striking.”

“0.25 kg of CO2-equivalent per person saved annually from reduced hospitalizations might sound small. However, when this figure is scaled up to the millions of patients eligible for these therapies, it adds up to over 2 billion kilograms of CO2-equivalent saved. Similar-scale reductions were observed in waste generation and water use. This research highlights how even modest incremental individual gains can result in significant collective impact,” Dr Ganatra continued.

2 billion kg of CO2 is approximately equivalent to 20,000 full capacity Boeing 747 long-haul flights, or city-wide emissions from Brussels over 3 months. Around 30 million trees grown over 10 years would be needed to offset 2 billion kg of CO2.

The analysis also showed that those taking the GLP1-receptor antagonist treatment had approximately 695.33 kg CO2-equivalent lower emissions per patient per year due to a reduction in daily calorie consumption compared to placebo.

“By combining clinical trial data with environmental life cycle assessment metrics, we offer a new lens to evaluate the full impact of prescribing decisions. We also show that it is possible for medical treatments to deliver dual benefits-better health for patients and a healthier planet,” Dr Ganatra added. “We hope that in the future, policymakers will integrate sustainability metrics into health technology assessments, drug coverage decisions, and procurement frameworks.”

Each worsening heart failure event was assumed to involve one inpatient admission and a round trip to the hospital. Greenhouse gas emissions associated with the production and use of a GLP1 receptor agonist were obtained from a leading pharmaceutical drug manufacturer.

The study used modelling data from prior trials and established environmental life cycle assessment emissions data sets, rather than direct measurements. It could not take into account patient-level variability such as behavioural differences, and the research used mean values for hospital-related emissions.

“The next step for this research is to validate our modelling with real-world emissions data and clinical outcomes. In the future, we hope that environmental impact will be integrated into clinical trial designs, drug regulatory processes, and formulary decisions to ensure health systems align with planetary health goals,” Dr Ganatra concluded.

The findings from this study also support previous research that found that treatment of patients with GLP-1 receptor agonists reduced hospital visits for patients with heart failure with preserved ejection fraction.

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HCQ Plus Prednisolone Improves Outcomes in Inflammatory Cardiomyopathy: Study

Inflammatory cardiomyopathy, often following fulminant myocarditis, is characterized by myocardial inflammation, impaired cardiac function, and increased risk of heart failure. Effective management of this condition is essential to prevent long-term complications and improve patient survival. Traditional treatment approaches often focus on supportive care, but recent research has explored immunomodulatory therapies to directly target inflammation and preserve cardiac function.

A new study investigated the efficacy of a 12-month combination therapy with hydroxychloroquine (HCQ) and prednisolone in patients diagnosed with inflammatory cardiomyopathy. The study included patients who had experienced fulminant myocarditis and demonstrated reduced left ventricular function, elevated inflammatory markers, and clinical symptoms of heart failure. The intervention group received HCQ alongside a tapering regimen of prednisolone, while outcomes were monitored through cardiac imaging, laboratory markers, and patient-reported functional status.

Results showed that combination therapy significantly improved cardiac function, as measured by increased left ventricular ejection fraction and reduced ventricular dilation. Inflammatory markers, including C-reactive protein and cytokine levels, were markedly reduced, indicating effective suppression of myocardial inflammation. Patients also reported improved exercise tolerance and reduced fatigue, suggesting enhanced quality of life. Importantly, the treatment was well tolerated, with no serious adverse events reported, highlighting the potential safety of long-term HCQ and prednisolone therapy in this population.

The authors note that while these findings are promising, larger multicenter studies with longer follow-up are needed to confirm efficacy, optimize dosing, and fully evaluate long-term safety. Nevertheless, the study provides strong preliminary evidence that combining HCQ with prednisolone can be an effective strategy to manage inflammatory cardiomyopathy following fulminant myocarditis, addressing both inflammation and cardiac function.

Reference: He, W., Cui, G., Chen, J. et al. The efficacy and safety of hydroxychloroquine in patients with chronic inflammatory cardiomyopathy: a multicenter randomized study (HYPIC trial). BMC Med 23, 467 (2025). https://doi.org/10.1186/s12916-025-04301-w

Keywords: hydroxychloroquine, prednisolone, inflammatory cardiomyopathy, fulminant myocarditis, heart function, cardiac inflammation, immunomodulatory therapy, left ventricular ejection fraction, heart failure, Journal of Cardiac Failure, He, W., Cui, G., Chen, J

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Toripalimab-Based Cisplatin-Free Strategy Efficacious, safe in Advanced NPC: JAMA

Researchers have found in a phase 3 trial that toripalimab combination therapy without cisplatin proved feasible, offering high failure-free survival and low toxicity in locoregionally advanced nasopharyngeal carcinoma (NPC). This study was published in JAMA by The DIAMOND Study Group.

NPC is a cancerous tumor that originates from the nasopharynx and has a high incidence in East and Southeast Asia. Concurrent cisplatin-radiotherapy has long been standard treatment, but the toxicity of cisplatin, especially nausea, vomiting, and renal damage, usually constrains tolerability and impairs patients’ quality of life. This new phase 3 trial offers solid evidence that a cisplatin-sparing strategy can be as effective and safer.

This multicenter, open-label, randomized phase 3 clinical trial was carried out in 13 Chinese hospitals from August 2021 to July 2022.

  • Participants: 532 T4N1M0 or T1-4N2-3M0 NPC patients

  • Median age: 47 years (IQR, 39–54 years)

  • Women: 25.2%

Randomization:

  • Standard therapy group (n=266): toripalimab + gemcitabine-cisplatin induction chemotherapy + concurrent cisplatin-radiotherapy

  • Cisplatin-sparing group (n=266): same regimen without concurrent cisplatin

  • Toripalimab (240 mg) was administered every 3 weeks for a total of 17 cycles (3 induction, 3 concurrent with radiotherapy, and 11 adjuvant).

The coprimary outcomes were failure-free survival (noninferiority margin: 8%) and all-grade incidence of vomiting. Secondary outcomes were overall survival, recurrence-free survival, distant metastasis–free survival, safety, tumor response, quality of life, and tolerability.

Key Findings

With a median follow-up of 37 months (range, 4–50 months):

Failure-free survival (3-year rate):

  • Cisplatin-sparing group: 88.3%

  • Standard therapy group: 87.6%

  • Difference: 0.7% (1-sided 95% CI lower limit, −3.9%)

  • P = .002 for noninferiority (HR, 0.92; 95% CI, 0.66–1.79; log-rank P = 0.73)

Incidence of all-grade vomiting:

  • Cisplatin-sparing group: 26.2% (68/260)

  • Standard therapy group: 59.8% (156/261)

  • Difference: 33.6% (P < .001)

Quality of life:

  • Improved in cisplatin-sparing group, particularly in gastrointestinal symptoms, global health status, and functional scores

  • Patient-reported participation rates: 87.5% (QoL) and 94.7% (tolerability)

  • Overall survival and recurrence-free outcomes: Similar between groups

In this large phase 3 trial, toripalimab combined with induction chemotherapy and radiotherapy was found to be noninferior on survival outcomes and superior on safety and quality of life for advanced NPC. These results indicate that a cisplatin-sparing regimen could be a new standard of care, minimizing treatment burden without loss of efficacy.

Reference:

The DIAMOND Study Group. Toripalimab Combination Therapy Without Concurrent Cisplatin for Nasopharyngeal Carcinoma: The DIAMOND Randomized Clinical Trial. JAMA. Published online August 21, 2025. doi:10.1001/jama.2025.13205

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