Merck begins phase 3 trial of MK-1084, Keytruda combo for first-line treatment of certain patients with Metastatic Non-Small Cell Lung Cancer

Rahway: Merck, known as MSD outside of the United States and Canada, has announced it has initiated a Phase 3 clinical trial evaluating MK-1084, an investigational oral selective KRAS G12C inhibitor, in combination with KEYTRUDA for the first-line treatment of certain patients with metastatic non-small cell lung cancer (NSCLC) whose tumors harbor KRAS G12C mutations and express PD-L1 (tumor proportion score [TPS] ≥50%).

“KRAS is among the most prevalent mutations in cancer and KRAS G12C is the most common KRAS mutation in patients with non-small cell lung cancer,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “Based on early evidence showing MK-1084 in combination with KEYTRUDA had a manageable safety profile and promising anti-tumor activity, we are now proceeding to a larger Phase 3 trial to evaluate this combination in certain patients with metastatic non-small cell lung cancer.”

Merck has initiated a Phase 3, randomized, double-blind, multicenter clinical trial (NCT06345729) evaluating once daily MK-1084 in combination with KEYTRUDA administered once every three weeks compared with KEYTRUDA plus placebo in previously untreated patients with KRAS G12C-mutated metastatic NSCLC with a PD-L1 TPS ≥50%. The trial will enroll approximately 600 patients globally. The primary endpoints of the study are progression-free survival and overall survival, and key secondary endpoints include objective response rate and duration of response.

MK-1084 is currently being evaluated in a Phase 1, open-label multicenter clinical trial (NCT05067283) to assess safety, tolerability, pharmacokinetics and efficacy of MK-1084 as monotherapy and as part of various combination therapies in patients with KRAS G12C mutant advanced solid tumors. Preliminary safety and efficacy data from this trial were previously presented at the European Society for Medical Oncology (ESMO) Congress in 2023.

MK-1084 is being developed through a collaboration with Taiho Pharmaceutical Co. Ltd and Astex Pharmaceuticals (UK), a wholly owned subsidiary of Otsuka Pharmaceutical Co., Ltd. This collaboration was announced in January 2020.

MK-1084 is an investigational, potent and specific KRAS G12C covalent inhibitor. Mutations in KRAS are among the most prevalent mutations found in cancer, occurring with high frequency in non-small cell lung cancer, pancreatic, urogenital and colorectal cancers. The KRAS G12C mutation is the most frequently observed KRAS mutation in patients, occurring in approximately 14% of non-small cell lung cancers (adenocarcinoma). Despite decades of research and recognition of the therapeutic importance of targeting KRAS, the development of small molecule inhibitors targeting KRAS mutations has been challenging.

Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.

Read also: European Commission approves Merck Keytruda plus Chemotherapy for lung cancer

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Statins associated with new-onset diabetes in dose-dependent manner: Lancet

USA: A meta-analysis of individual participant data has shed light on the effects of statin therapy on diagnoses of new-onset diabetes and worsening glycemia in large-scale randomized blinded statin trials.

The study findings, The Lancet Diabetes & Endocrinology, reaffirm a dose-dependent association between statin therapy, which may be relevant for guidelines and shared decision-making. However, these glycaemic effects do not outweigh the statin therapy benefit among individuals for whom they are recommended.

“Statins cause a moderate dose-dependent increase in new diabetes diagnoses that are consistent with a small upward shift in glycemic, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes,” the researchers wrote.

“Importantly, however, any theoretical adverse effects of statins on the cardiovascular (CV) risk that might arise from these small increases in glycemia are already accounted for in the overall reduction in CV risk seen with statin therapy in these trials.”

Previous meta-analyses of summary data from randomized controlled trials (RCTs) have revealed that stating therapy raises the risk of diabetes, however, not much is known about the timing or size of this effect, or who is at greatest risk. To fill this knowledge gap, Christina Reith and colleagues from Cholesterol Treatment Trialists’ (CTT) Collaboration, analyzed individual participant data from large, long-term, randomized, double-blind trials of statin therapy.

For this purpose, the researchers conducted a meta-analysis of individual participant data from RCTs of statin therapy that participated in the CTT Collaboration. The meta-analysis included double-blind RCTs of statin therapy of at least 2 years’ scheduled duration and with at least 1000 participants. All recorded diabetes-related adverse events, measures of glycemia, and treatments were sought from eligible trials.

Meta-analyses assessed the effects of allocation to statins on new-onset diabetes and on worsening glycemia in people with diabetes. New-onset diabetes was defined as the use of new glucose-lowering medications, diabetes-related adverse events, glucose concentrations, or HbA1c values.

Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123 940 participants, 21% with diabetes; median follow-up of 4·3 years), and four trials compared more versus less intensive statin therapy (30 724 participants, 17% with diabetes, median follow-up of 4·9 years).

The study led to the following findings:

  • Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes, and allocation to high-intensity statin therapy resulted in a 36% proportional increase.
  • For each trial, the rate of new-onset diabetes among participants allocated to receive a placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than in the low-intensity or moderate-intensity trials.
  • The main determinant of the magnitude of the absolute excesses in the two types of trials was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy.
  • In participants without baseline diabetes, mean glucose increased by 0·04 mmol/L with both low-intensity or moderate-intensity and high-intensity statins, and mean HbA1c increased by 0·06% with low-intensity or moderate-intensity statins and 0·08% with high-intensity statins.
  • Among those with a baseline measure of glycemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution.
  • The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time.
  • Among participants with baseline diabetes, the RRs for worsening glycemia were 1·10 for low-intensity or moderate-intensity statin therapy and 1·24 for high-intensity statin therapy compared with placebo.

In conclusion, among individuals without diabetes, statin therapy produces a dose-dependent rise in the rate of diabetes diagnosis by inducing a small increase in glycemia. People are most at risk of exceeding the diagnostic threshold for diabetes due to statins if their glycaemic control is close to the threshold before treatment.

“The diabetes-related risks arising from the small changes in glycemia resulting from statin therapy greatly outweighed the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration,” the researchers wrote.

Reference:

Cholesterol Treatment Trialists’ (CTT) Collaboration. Electronic address: ctt@ndph.ox.ac.uk; Cholesterol Treatment Trialists’ (CTT) Collaboration. Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Lancet Diabetes Endocrinol. 2024 Mar 26:S2213-8587(24)00040-8. doi: 10.1016/S2213-8587(24)00040-8. Epub ahead of print. PMID: 38554713.

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KGMU Trauma Centre to get pneumatic tube conveyor system for transporting samples

Lucknow: The trauma centre at King George’s Medical University (KGMU) is set for a significant upgrade with the introduction of a pneumatic tube conveyor network system. 

This innovative system is designed to revolutionize the transportation of blood samples and other specimens between wards and the laboratory, promising to drastically reduce time and effort. 

Vice-chancellor Soniya Nityanand has announced the commencement of the project, which has been allocated a budget of Rs 80 lakhs. The primary goal is to enhance sample delivery efficiency and expedite the diagnostic process at KGMU. The pneumatic tube system will propel sample capsules through a network of tubes using pressurized air, eliminating the need for manual transportation.

Also Read:KGMU to kickstart its kidney transplant programme, once again

According to an IANS report, “Attendants of patients or lab attendants in the wards take blood samples of admitted patients to the labs. They will no longer need to run from ward to lab to submit the samples,” said Nityanand.

She said, “The pneumatic tube system will use pressurised air to propel sample capsules through a network of tubes, significantly reducing transportation time and effort. It will also save manpower required for collecting samples from the ward.”

This will be a welcome relief for the trauma centre, which caters to a high volume of patients (around 300-400 daily) and keeps the labs busy round-the-clock.

“With multiple tests required for each patient, attendants often face long wait times while navigating between departments. The new system will free them up to focus on patient care,” she added.

Additionally, KGMU is introducing an online payment system to further improve patient experience. Patients can deposit an estimated amount against their central registration number, with fees for diagnostic tests automatically deducted.

This initiative aims to streamline the billing process and shorten waiting times at payment counters.

“Both patients and attendants will benefit tremendously from saved time and energy,” said Chief Medical Superintendent Sandeep Tiwari. The project is expected to be completed within 3-4 months after the tender process.

Also Read:Paediatric trauma section to be set up at KGMU

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Novel lateral flow assay rapid and cost-effective point-of-care test for diagnosis of Neisseria gonorrhoeae: Lancet

Effective control of Neisseria gonorrhoeae (N. gonorrhoeae) relies on rapid and accurate diagnostic tests. The World Health Organization (WHO) and Foundation for Innovative New Diagnostics (FIND) have established criteria for a non-molecular rapid point-of-care test, emphasizing the need for high sensitivity and specificity, quick turnaround time, and affordability. A novel lateral flow assay (NG-LFA) has been developed to meet these requirements.

In a recent cross-sectional study conducted in South Africa, researchers evaluated the performance of the NG-LFA at primary health-care facilities. This study was published in The Lancet journal. The study was conducted by Prof. Remco and colleagues.

Male patients with urethral discharge syndrome and female patients with vaginal discharge syndrome were recruited from five health facilities. First-void urine specimens and nurse-collected vaginal swabs were tested in-facility with the NG-LFA and Xpert CT/NG PCR assay. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was performed on all LFA-positive specimens.

The key findings of the study were as follows:

• Between March 7 and September 19, 2022, 200 male patients and 200 female patients were enrolled, with median ages of 24 years and 25 years, respectively.

• Additionally, 23 male patients and 12 female patients with partner notification slips were enrolled.

• The NG-LFA demonstrated a sensitivity of 96.1% in urine specimens and 91.7% in vaginal swabs, with specificities of 97.2% and 96.3%, respectively.

• NG-MAST analysis revealed 93 different sequence types among LFA-positive specimens.

The study implicated that novel NG-LFA exhibited excellent clinical sensitivity and specificity in symptomatic male and female patients, meeting the criteria set forth in the target product profile. This assay could serve as a valuable tool for optimizing clinical management and reducing unnecessary antibiotic use, particularly in settings with limited access to laboratory testing.

The NG-LFA presents a promising advancement in the diagnosis of N. gonorrhoeae infections, offering high sensitivity and specificity in symptomatic patients. Its implementation could lead to more effective management strategies and contribute to the global efforts to combat gonorrhea.

Reference:

Peters, R. P. H., Klausner, J. D., Mazzola, L., Mdingi, M. M., Jung, H., Gigi, R. M. S., Piton, J., Daniels, J., de Vos, L., Adamson, P. C., Gleeson, B., & Ferreyra, C. (2024). Novel lateral flow assay for point-of-care detection of Neisseria gonorrhoeae infection in syndromic management settings: a cross-sectional performance evaluation. Lancet, 403(10427), 657–664. https://doi.org/10.1016/s0140-6736(23)02240-7

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Bariatric artery embolization may improve weight loss in obesity patients, claims study

A recent clinical trial named BEATLES showed the potential of the procedure known as bariatric arterial embolization (BAE) using novel, custom-engineered radiopaque microspheres, BTG-001933 that was developed by Boston Scientific. The key findings of this study were presented in the SIRpass summit and the abstract was published in the Journal of Vascular and Interventional Radiology

This study was designed to evaluate the safety and efficacy of this innovative treatment in patients with obesity. The BEATLES trial was approved by both the Institutional Review Board (IRB) and the FDA to explore an alternative solution for weight loss in patients with class II-III obesity. This trial commenced in October 2020 included individuals of 21 to 70 years with a Body Mass Index (BMI) of ≥35 kg/m^2 and weighing ≤400 lbs.

The procedure involves the embolization of the left gastric artery and in some cases, the gastroepiploic artery by utilizing BTG-001933 microspheres that are 100-200µm in size. This technique aimed to reduce blood flow to the stomach by decreasing hunger and promoting weight loss. The pilot phase of the clinical trial concluded with a one-year follow-up in December 2023, revealing promising outcomes.

The trial reported 100% technical success in the procedures performed on ten participants, with no major adverse events observed. Minor complications included a healing mucosal ulcer and a vascular access site pseudoaneurysm and deemed unrelated to the procedure. Also, the participants showed significant weight loss and BMI reduction over the 12-month period where the MRI scans indicated a reduction in subcutaneous and intra-muscular fat while preserving the muscle mass.

This approach highlights the potential for significant weight loss and emphasizes the importance of muscle preservation during the process. The use of BTG-001933 microspheres demonstrates increased efficacy when compared to the other embolic agents used in previous studies that offer a safer and more effective treatment option for severe obesity.

The BEATLES trial paves the way for effective obesity management that suggests BAE could soon become a potential alternative for the individuals who seek muscle-sparing weight loss. Further research and larger trials are mandated to confirm these findings and potentially offer a new lease on life for individuals with obesity.

Reference:

Khalil, A., Bosworth, E., Giraldo Herrera, D., Memenza, R., Yuan, F., Linge, J., Holly, B., Liddell, R., & Weiss, C. (2024). Abstract No. 218 Bariatric Embolization of ArTeries with imaging visibLe EmbolicS (BEATLES): Pilot Study. In Journal of Vascular and Interventional Radiology (Vol. 35, Issue 3, pp. S98–S99). Elsevier BV. https://doi.org/10.1016/j.jvir.2023.12.259

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Long-term progesterone use increase intracranial meningioma risk in women: BMJ

A comprehensive national case-control study conducted in France revealed a significant link between the use of specific progestogen-based medications and a higher risk of developing intracranial meningioma. The key findings were published in the British Medical Journal.

This research utilized data from the French National Health Data System and scrutinized the health records of over 108,000 women by focusing on 18,061 cases who underwent brain surgery for meningioma from January 2009 to December 2018.

The study meticulously matched each patient case with five control subjects after adjusting for year of birth and area of residence to ensure the reliability of the findings. The outcome of this study evaluated the use of various progestogens that included progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest and levonorgestrel intrauterine systems by determining exposure based on at least one dispensation of the drug within the year preceding the index date.

In the users of medrogestone, medroxyprogesterone acetate (injectable) and promegestone the findings unveiled a marked increased risk of meningioma associated with prolonged use (≥one year) of these medications. Medrogestone users expressed a 3.49 times higher risk, while the injectable medroxyprogesterone acetate users showed a 5.55 times increased risk and the promegestone users had a 2.39 times increased risk of developing the brain tumor when compared to non-users.

Also, the study provided some potential outcomes for users of progesterone, dydrogesterone and levonorgestrel intrauterine systems that indicated no additional risk of meningioma associated with these specific progestogens. The results concerning dienogest and hydroxyprogesterone were inconclusive due to insufficient data.

As part of the study, certain medications were utilized as positive controls due to their known association with meningioma risk. Cyproterone acetate, nomegestrol acetate, and chlormadinone acetate were among these, with findings supporting the elevated risk previously identified, further validating the study’s methodology and outcomes.

The revelations from this extensive research are particularly concerning given the widespread use of medroxyprogesterone acetate as a contraceptive method. The study calls for heightened awareness among healthcare providers and patients regarding the potential risks associated with prolonged use of certain progestogens. The findings of this study underline the importance of individual risk assessment in the prescription of progestogen-based medications which calls for a more careful approach in their use, especially in women at risk for intracranial meningiomas.

Reference:

Roland, N., Neumann, A., Hoisnard, L., Duranteau, L., Froelich, S., Zureik, M., & Weill, A. (2024). Use of progestogens and the risk of intracranial meningioma: national case-control study. In BMJ (p. e078078). BMJ. https://doi.org/10.1136/bmj-2023-078078

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Preheated thermoviscous composite resin useful option for restoring noncarious cervical lesions restorations: Study

Preheated thermoviscous composite resin useful option for restoring noncarious cervical lesions restorations suggests a new study published in the Journal of Dentistry.

This 24-month, double-blind, split-mouth randomized clinical trial aimed to compare the retention rates of a preheated thermoviscous composite resin (PHT) compared to a non-heated composite resin (NHT) in non-carious cervical lesions (NCCLs). A total of 120 restorations were restored on NCCLs using a preheated (VisCalor bulk, Voco GmbH) and a non-heated (Admira Fusion, Voco GmbH) composite resins with 60 restorations per group. A universal adhesive in the selective enamel conditioning was applied. In the PHT group, the composite was heated at 68 °C for using a bench heater. In the NHT group, no heating was employed. Both restorative materials were dispensed into caps and inserted into the NCCLs. The restorations were evaluated at baseline, 6, 12, 18, and after 24 months of clinical service using the FDI criteria. Statistical analysis was performed with Kaplan–Meier estimation analysis for retention/fracture rate and Chi-square test for the other FDI parameters (α=0.05).

Results: After 24 months 108 restorations were assessed. Seven restorations were lost (two for PHT group and five for NHT group), and the retention rates (95 % confidence interval [CI]) were 96.7 % (81.5–99.9) for PHT group and 90.8 % (81.1–96.0) for NHT group, with no statistical differences between them (p > 0.05). The hazard ratio (95 % CI) was 0.52 (0.27 to 1.01), with no significant difference within groups. In terms of all other FDI parameters that were assessed, all restorations were deemed clinically acceptable. Both composites showed high rates of retention rates after 24 months. The clinical performance of the new preheated thermoviscous was found to be as good as the non-heated composite after 24-month of clinical evaluation in non-carious cervical lesions.

Reference:

Michael Willian Favoreto, Taynara de Souza Carneiro, Romina Ñaupari-Villasante, Deisy Cristina Cordeiro, Gabriel David Cochinski, Thais Vilalba Paniagua Machado do Nascimento, Thalita de Paris Matos, Matheus Coelho Bandeca, Alessandra Reis, Alessandro D. Loguercio. Clinical performance of preheating thermoviscous composite resin for non-carious cervical lesions restoration: A 24-month randomized clinical trial. Journal of Dentistry, Volume 144, 2024, 104930, ISSN 0300-5712, https://doi.org/10.1016/j.jdent.2024.104930.

(https://www.sciencedirect.com/science/article/pii/S0300571224001003)

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Intake of arachidonic acid and other fatty acids may increase risk of total hip arthroplasty: Study

Intake of arachidonic acid and other fatty acids may increase the risk of total hip arthroplasty suggests a new study published in the Arthritis Care and Research.

The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk for total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women. This was a prospective analysis of 34,990 women in the Women’s Health Initiative (WHI). Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a sub-cohort of 3428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazard models were constructed to estimate risk of arthroplasty.

Results: Risk of THA was associated with higher intake of arachidonic acid, [multivariable hazard ratio (HR) quartile (Q)4 vs Q1: 1.16; 95% CI: 1.01, 1.34; p for linear trend = 0.03] and higher intake of eicosapentaenoic acid + docosahexaenoic acid [(EPA+DHA), HR Q4 vs Q1: 1.20; 95% CI:1.05, 1.39; p for linear trend=0.003]. There was a linear trend (p=0.04) for a higher risk of THA with higher erythrocyte EPA+DHA in BMI-adjusted models; however, there was no significant difference in THA by quartiles of erythrocyte EPA+DHA (p=0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA. Higher baseline intakes of arachidonic acid and EPA+DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and TKA. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk.

Reference:

Orchard, T., McLaughlin, E., Winschel, T., Shadyab, A., Laddu, D., Vitolins, M., Florina, C. and Jackson, R. (2024), Fatty acid intake and polyunsaturated fatty acid biomarkers and risk of total knee or hip arthroplasty among older women in the Women’s Health Initiative. Arthritis Care Res. Accepted Author Manuscript. https://doi.org/10.1002/acr.25319

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Blood test can predict risk of relapse in advanced bladder cancer patients following surgery, suggests study

Testing for tumour DNA in the blood can successfully identify advanced bladder cancer patients who will not relapse following surgery, new research shows.

This could allow doctors to target treatments more effectively to those who need it, and spare those patients for whom further treatment is unnecessary, researchers say.

The findings from the screening phase of the IMvigor011 Phase III trial are presented today [Friday 5 April] at the European Association of Urology Congress in Paris.

They show that just over 90% of muscle invasive bladder cancer (MIBC) patients with a negative circulating DNA (ctDNA) test following surgery, which remained negative on follow up, did not relapse. The findings mean that use of a ctDNA test could allow some patients to be spared further treatment with minimal risk.

MIBC is an advanced form of bladder cancer, where the tumour has spread into the bladder wall. The disease is usually treated by surgery to remove the bladder. Around half of patients see cancer return, often in the lungs and usually within two-to-three years. All patients are currently offered follow-up treatment such as chemotherapy or immunotherapy to prevent recurrence, for which the side effects can be serious and lifechanging.

Other Phase III trial results, also presented at the EAU Congress today, show that patients given immunotherapy, nivolumab, as a follow up to surgery have an average survival of nearly six years, compared to four for patients on placebo.

The CheckMate 274 trial has already shown that nivolumab can reduce recurrence of disease, but these interim results are the first to show the potential benefit in overall survival for MIBC patients.

Joost Boormans, Professor of Urology at Erasmus University Medical Centre in Rotterdam, and member of the EAU Scientific Congress Office, is chairing the session where both trials will present their findings. He said:

“Although we already knew that nivolumab improved disease-free survival in MIUC patients who received radical surgery, overall survival is what really matters following local treatment, such as radical surgery. These interim findings, which show that overall survival also improves, are very encouraging, particularly as this hasn’t been the case in other recent immunotherapy trials.

“The question for regulators and healthcare authorities is whether the improvement in overall survival is enough to justify licensing or prescribing the drug for all patients, in the knowledge that some of these patients would have been cured of their cancer by surgery alone. This is where the findings from the IMvigor011 trial could really make a difference, by allowing us to select patients at highest risk who will benefit the most from treatment while sparing others for whom it isn’t needed.

“At a time when healthcare resources are under pressure, this kind of innovation is really needed.”

IMvigor011

IMvigor011 is a global, double-blind, randomised Phase III trial looking at the efficacy of the immunotherapy atezolizumab vs placebo in patients with high-risk MIBC.

The trial is recruiting MIBC patients post-surgery and testing their blood for circulating tumour DNA. Those with a positive ctDNA result are randomised to receive either atezolizumab or placebo. Those with a negative result are given no further treatment, but were followed up with scans and further ctDNA tests for up to two years. For the analysis presented at the EAU Congress today, 171 patients with a negative ctDNA test were included, with follow up continuing on a further 115.

Just 17 patients of the 171 patients (9.9%) saw their cancer return within two years. These outcomes were irrespective of the stage their tumour was at or whether it showed elevated levels of PD-L1, a protein biomarker that plays a role in cancer.

Professor Thomas Powles of Barts Cancer Institute leads the IMvigor011 trial. He said: “These results are even better than we were hoping. The risk of relapse in this ctDNA group of patients is just 1 in 10. It appears this test can effectively filter patients into two groups: those who are likely to relapse and those at much lower risk. Focusing treatment on those at risk and sparing the very low risk group potentially life-altering treatment-related side effects is attractive. Hopefully these data will allow patients to remain treatment free with the reassurance they need, that they’re unlikely to see their cancer return.”

The study is sponsored by F. Hoffmann-La Roche Ltd.

CheckMate 274

CheckMate 274 is a global, Phase III, randomised, double-blind trial of nivolumab vs placebo in high-risk MIBC after surgery.

The trial recruited just over 700 patients, with half given nivolumab and the other half given a placebo every two weeks for 12 months following an operation to remove the bladder. Patients were also tested to see if their cancer had elevated levels of the biomarker PD-L1, which nivolumab specifically targets.

The trial has already reported positive results in preventing recurrence, particularly for PD-L1 patients. Across all patients, those on nivolumab had an average of 22 months before recurrence, compared to 10 months for those on placebo. However, of the PD-L1 group, those on nivolumab had an average of over four years without recurrence, compared to just over eight months for those on placebo.

The latest results, although still early stage, show a similar benefit in overall survival. For all patients, those on nivolumab survive on average for nearly six years (69.5 months) compared to just over four years (50.1 months) for those on placebo. The researchers do not yet have enough follow-up data to separate out the PD-L1 patients, but the analysis so far shows that overall survival is likely to also be even better for this group when treated with nivolumab versus placebo.

Professor Matthew Galsky from the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York, leads the CheckMate 274 trial. He said: “We know that patients with high-risk urothelial cancer are at highest risk for recurrence within the first three years after surgery. We’ve now followed a substantial subset of patients for longer than that on this study without recurrence. It looks as if the improvement in disease free survival is ultimately going to translate into improvement in overall survival. And that’s for all patients, but particularly patients with the PD-L1 biomarker. Our hope is that this improvement will then translate into an increased likelihood of curing cancer in these patients.”

Reference:

Bladder cancer treatment can be better targeted and more effective, trials show, European Association of Urology, Meeting: EAU24 European Association of Urology Congress.

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Somatropin Shows Long-Term Safety and Effectiveness in Pediatric Patients with growth hormone deficiency: Study

A recent study found Omnitrope (somatropin) to be effective and safe in pediatric patients over long term. The findings from the PATRO Children study were published in the journal of Drug Design, Development and Therapy.

Amidst the ongoing concerns over the safety and effectiveness of pediatric treatments, Omnitrope® (somatropin) which is a biosimilar recombinant human growth hormone (rhGH) showed positive outcomes. The latest data from the PATRO Children study highlights its remarkable performance in real-world clinical settings.

The PATRO Children study was conducted to monitor the long-term safety and efficacy of Omnitrope® and enrolled a substantial cohort of 7359 pediatric patients, majority of whom were treatment-naïve. The results underline the well-tolerated nature of this treatment with a notable 86.0% of patients being new to therapy at the onset of the study.

Growth hormone deficiency was found to be the predominant indication for treatment, that was followed closely by patients born small for gestational age (SGA). Throughout the study duration, the patients expressed a sustained catch-up growth with the standard deviation scores (SDS) of height significantly improving over time.

Despite the concerns inherent to any therapeutic intervention, the adverse events (AEs) associated with Omnitrope® were largely mild to moderate in severity that reaffirms its favorable safety profile. A mere 8.3% of patients experienced AEs suspected to be treatment-related, with commonly reported issues including headaches and injection-site discomfort. The low incidence rates of significant complications such as type 2 diabetes mellitus and primary malignancies further consolidated the safety credentials of this treatment.

Source:

Loche, S., Kanumakala, S., Backeljauw, P., Schwab, K., Lechuga-Sancho, A., Esmael, A., Urosevic, D., Boldea, A., & Zabransky, M. (2024). Safety and Effectiveness of a Biosimilar Recombinant Human Growth Hormone in Children Requiring Growth Hormone Treatment: Analysis of Final Data from PATRO Children, an International, Post-Marketing Surveillance Study. In Drug Design, Development and Therapy: Vol. Volume 18 (pp. 667–684). Informa UK Limited. https://doi.org/10.2147/dddt.s440009

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