Neoadjuvant Immunotherapy for Mismatch Repair Deficient Colon Cancer: Redefining Treatment
Locally advanced DNA mismatch repair-deficient (dMMR) colon cancer accounts for up to 15% of nonmetastatic colon cancers. These tumors are typically managed similarly to mismatch repair-proficient tumors, with surgery followed by adjuvant chemotherapy. However, recent studies, including the NICHE-2 trial, suggest potential benefits of immunotherapy over chemotherapy in this patient population.
READ MORE...
The NICHE-2, a phase 2, multicenter, single-group study, conducted by the Netherlands Cancer Institute, aimed to evaluate the safety and efficacy of neoadjuvant therapy using a combination of nivolumab (a programmed cell death 1 [PD-1] inhibitor) and ipilimumab (a cytotoxic T-lymphocyte antigen 4 [CTLA-4] inhibitor) in patients with unresected, locally advanced dMMR colon cancer. The study, which ran from July 2017 to July 2022, enrolled 115 patients (median age, 60 years; 58% women) with stage II or III disease, confirmed as resectable with no distant metastases. Patients received 4-weeks of neoadjuvant treatment (2-week cycles, with treatment at the start of each cycle) prior to surgery. Primary end points of the study were timely surgery (delay of no more than 2 weeks) and 3-year disease-free survival.
Key findings from NICHE-2 included a high pathologic response rate: 98% of patients showed some degree of pathologic response to the immunotherapy regimen, affording them a timely surgery, with 68% achieving a pathologic complete response (no residual viable tumor in the tumor bed or lymph nodes). Importantly, no disease recurrences were observed during the study's follow-up period (median, 26.2 months), suggesting promising long-term disease control outcomes. This contrasts with historic recurrence rates seen in dMMR colon cancer despite adjuvant chemotherapy.
The safety profile of the regimen was also assessed, with most adverse events being manageable grade 1 or 2 immune-related adverse events. Grade 3 or 4 adverse events occurred in a small percentage of patients and were generally reversible.
The NICHE-2 trial contributes significant evidence supporting the use of neoadjuvant PD-1 and CTLA-4 inhibitors in locally advanced dMMR colon cancer, potentially redefining standard treatment for this subset of patients. (Chalabi, M., et al. (2024). Neoadjuvant immunotherapy in locally advanced mismatch repair-deficient colon cancer. N Engl J Med, 390, 1949-1958. Retrieved June 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2400634)
Released: July 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
Peceleganan Spray for Skin Wound Infections
Skin wound infections are typically treated with antibiotics, but frequent use of these drugs can cause antibiotic resistance. As a result, antimicrobial peptides (AMPs), like peceleganan (PL-5), have been considered as an alternative treatment option for skin wound infections. AMPs work via nonspecific mechanisms of disrupting bacterial cells, which reduces the likelihood of antibiotic resistance.
READ MORE...
In a phase 3 clinical trial conducted across 37 hospitals in China, PL-5 spray was evaluated for its efficacy and safety in treating skin wound infections compared to silver sulfadiazine (SSD) cream, a conventional topical antibiotic. The trial enrolled 570 patients, ages 18 to 75, with secondary open wound infections randomized to receive either 2% peceleganan spray (n = 381) or 1% SSD cream (n = 189). The primary endpoint, clinical efficacy rate on day 8, showed that 90.4% of patients treated with PL-5 achieved clinical efficacy compared to 78.7% in the SSD group, a statistically significant difference. Although SSD showed higher rates of bacterial clearance (46.0%) compared to PL-5 (24.0%), PL-5 still exhibited substantial effectiveness against common wound pathogens like Staphylococcus aureus and Pseudomonas aeruginosa.
Safety evaluations indicated that PL-5 spray had a comparable incidence of adverse events to SSD cream, with no unexpected safety issues reported. Both treatments were well-tolerated among the study population, which included diverse wound types, such as burns, physical injuries, and diabetic foot ulcers.
Overall, PL-5 spray demonstrated promising clinical efficacy and safety in treating skin wound infections, likely due to its unique antimicrobial action against a broad spectrum of bacteria, including drug-resistant strains. Further research is recommended to explore its mechanism of action and optimize its clinical applications, possibly expanding its role in wound care management. (Wei, Y., et al. (2024). Peceleganan spray for the treatment of skin wound infections: A randomized clinical trial. JAMA Netw Open, 7(6), Article e2415310. Retrieved June 2024 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2819836)
Released: July 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
Linvoseltamab: A Different Approach to Treating Relapsed and Refractory Multiple Myeloma
Multiple myeloma remains incurable despite advances in therapies, and there is a need for treatments that produce deep and long-lasting remissions, especially in patients who are resistant to current standard therapies. Linvoseltamab, a B-cell maturation antigen (BCMA)xCD3 bispecific antibody, which has shown antitumor activity in previous studies, has been suggested as a possible treatment option for relapsed and refractory multiple myeloma (RRMM).
READ MORE...
LINKER-MM1, an open-label, phase 1/2 clinical trial, sought to evaluate the efficacy of linvoseltamab in treating RRMM. The trial was conducted at 23 centers in multiple countries between January 2019 and October 2022 and included 282 patients (median age, 70) with triple-class refractory multiple myeloma. Phase 1 and 2 of the trial treated patients with varying doses of linvoseltamab (ranging from 3 mg to 800 mg) for a minimum of 24 weeks, and evaluated overall response rate, duration of response, and progression-free survival.
Results showed that the optimal dose of linvoseltamab was 200 mg, which provided an overall response rate of 70.9%, with 63.2% of patients achieving very good partial response or better, and 49.6% achieving complete response. Responses were rapid and long-lasting, with a median time of response of 29.4 months and a progression-free survival not reached at the data cutoff. Safety profiles indicated mild to moderate adverse events. Infections were common but decreased over time, especially among patients achieving deep responses.
The outcomes of this study support linvoseltamab as a valuable addition to the treatment landscape for multiple myeloma, offering deep and durable responses with a manageable safety profile compared to other BCMA-targeted therapies. (Bumma, N., et al. (2024). Linvoseltamab for treatment of relapsed/refractory multiple myeloma. Journal of Clinical Oncology. Advanced online publication. Retrieved June 2024 from https://ascopubs.org/doi/10.1200/JCO.24.01008)
Released: July 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
Tirzepatide Shows Promise in Managing Obstructive Sleep Apnea
Obstructive sleep apnea (OSA), characterized by disrupted breathing during sleep, is linked to cardiovascular complications, often exacerbated by excess weight. Traditional treatments, like positive airway pressure (PAP), have limitations in adherence and long-term effectiveness, prompting exploration of pharmaceutical interventions, like the GLP-1 receptor agonist, tirzepatide.
READ MORE...
SURMOUNT-OSA, comprised of two 52-week, phase 3 clinical trials, was conducted from June 2022 to March 2024 at 60 sites in multiple countries to assess tirzepatide as a treatment option for moderate-to-severe sleep apnea in those who are obese. The trials enrolled 469 participants either not using PAP (trial 1, 234 participants) or currently using PAP (trial 2, 235 participants) and randomized them to receive either tirzepatide (2.5 mg once weekly, then 2.5-mg dose increase every 4 weeks until week 20) or placebo for 52 weeks. The primary endpoint was the change in apnea-hypopnea index (AHI), with secondary endpoints including changes in body weight, hypoxic burden, inflammatory markers, and blood pressure. Baseline characteristics showed high AHI levels (average 51.5 to 49.5 events per hour) and severe obesity (average BMI 39.1 to 38.7).
Results demonstrated significant reductions in AHI with tirzepatide compared to placebo in both trials: −20.0 to −23.8 events per hour. Secondary endpoints, such as body weight, high-sensitivity C-reactive protein concentration, and systolic blood pressure also showed improvements with tirzepatide. Adverse events, predominantly gastrointestinal, were mostly mild to moderate and occurred more frequently during dose escalation.
These findings support further research of GLP-1 receptor agonists, such as tirzepatide, as a treatment option for OSA in individuals with obesity, addressing both sleep-related and cardiovascular risks associated with the condition. (Malhotra, A., et al. (2024). Tirzepatide for the treatment of obstructive sleep apnea and obesity. NEJM. Advanced online publication. Retrieved June 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2404881)
Released: July 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer