Two-drug Regimen Research Articles

Efficacy and safety of multi-day antiemetic treatment for patients undergoing multi-day chemotherapy: a systematic review of Clinical Practice Guidelines for Antiemesis 2023 from Japan Society of Clinical Oncology.

A standardized multi-day antiemetic regimen for multi-day chemotherapy remains elusive. This systematic review evaluated the efficacy and safety of multi-day antiemetic regimens in patients undergoing multi-day intravenous chemotherapy. We conducted a comprehensive search of PubMed, Cochrane Library, and Ichushi-Web databases for relevant studies published from January 1990 to December 2020. We included studies comparing multi-day and single-day antiemetic regimens for preventing chemotherapy-induced nausea and vomiting. No studies directly comparing multi-day versus single-day antiemetic regimens were found. Despite expanding control group criteria beyond "single-day antiemetic therapy" limited high-quality studies and variations in cancer types, chemotherapy regimens, and antiemetic treatments precluded meta-analysis. Among the included studies, some randomized controlled trials (RCTs) focused on complete response and vomiting rates. Two studies comparing two- and three-drug combinations reported higher complete response and no-vomiting rates with the three-drug regimen. Limited RCTs explored "nausea control" and "cost," and assessing "adverse events" proved challenging due to inconsistent reporting. The research on multi-day antiemetic therapy is limited, necessitating further investigation. Nonetheless, our findings suggest that three-drug combination therapy, including aprepitant, may offer superior antiemetic efficacy compared to two-drug regimens. Multi-day antiemetic therapy is strongly recommended during multi-day intravenous administration of cytotoxic anticancer drugs.

Neoadjuvant Chemotherapy for Borderline Resectable Head and Neck Cancers: A Comparative Study of Three-Drug and Two-Drug Regimens in a Low- and Middle-Income Country (LMIC) Context.

Background Borderline resectable head and neck squamous cell carcinoma (HNSCC) presents a significant therapeutic challenge, particularly in low- and middle-income countries (LMICs) like India. Neoadjuvant chemotherapy (NACT) aims to downstage tumors to achieve operability, but the optimal regimen remains controversial due to varying efficacy and toxicity profiles. This study compares the efficacy and toxicity of a three-drug regimen (TPF: docetaxel, cisplatin, and 5-fluorouracil) with a two-drug regimen (taxane and platinum) in patients with borderline resectable HNSCC in an LMIC setting. Methods In this retrospective cohort study, a total of 90 patients with borderline resectable HNSCC were included. Forty-three patients received the TPF regimen (Arm A), while 47 received the taxane + platinum regimen (Arm B). The outcomes measured included conversion to operability, stage-specific outcomes, overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Statistical analyses included chi-square tests for categorical variables, Kaplan-Meier survival analysis, and Cox proportional hazards modeling for multivariate analysis. Results The conversion to operability was significantly higher in the TPF group (72% vs. 51%, p=0.03). Patients in Arm A also exhibited a trend toward higher pathological complete response (pCR) rates compared to Arm B (60% vs. 43%, p=0.08). The overall survival and progression-free survival were improved in the TPF group, although the study did not reach statistical significance in these endpoints due to the limited sample size. However, the TPF regimen was associated with significantly higher toxicity. Grade 3-4 neutropenia occurred in 55% of the patients in Arm A compared to 32% in Arm B (p=0.01), and mucositis was observed in 47% of Arm A patients compared to 19% in Arm B (p=0.002). Febrile neutropenia was also more frequent in the TPF group (28% vs. 13%, p=0.04). Multivariate analysis identified the chemotherapy regimen (HR=1.45, 95% CI 1.05-2.01, p=0.02) and baseline nutritional status (HR=1.78, 95% CI 1.12-2.82, p=0.01) as independent predictors of overall survival. Conclusion While the TPF regimen offers superior efficacy in terms of tumor downstaging and conversion to operability, its higher toxicity profile limits its applicability in resource-constrained settings, such as LMICs. The taxane + platinum regimen, although less effective in downstaging, presents a more favorable toxicity profile, making it a viable alternative for patients with comorbidities or poor performance status. The choice between these regimens should be individualized, considering the patient's overall health, nutritional status, and the availability of supportive care. Further research is warranted to optimize NACT strategies for patients in LMICs.

Effects of switching to dolutegravir/lamivudine from tenofovir alafenamide fumarate/emtricitabine/dolutegravir or abacavir/lamivudine/dolutegravir on body weight and lipid profile in Japanese people living with HIV

BackgroundThe two-drug regimen of dolutegravir/lamivudine (DTG/3TC) is currently an optional antiretroviral therapy (ART). Despite its reported advantages on body weight and lipid profile, the same effects have not yet been reported for Asian population. MethodsWe conducted a single-center retrospective study involving Japanese people living with HIV (PLWH). They were divided into four groups: those who had received abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) and continued the same (ABC-ON group) or switched to DTG/3TC (ABC-OFF group), those who had received tenofovir alafenamide fumarate/emtricitabine/dolutegravir (TAF/FTC/DTG) and continued the same (TAF-ON group) or switched to DTG/3TC (TAF-OFF group). We compared changes in viral load, CD4⁺ cell count, CD4⁺/CD8⁺ ratio, body weight, BMI, lipid profiles, estimated glomerular filtration rate (eGFR), and fibrosis index based on four factors (FIB4-index) between the pre-switch and post-switch period. ResultsOf the 541 PLWH on DTG-based ART, 165, 94, 264 and 18 constituted the ABC-ON, ABC-OFF, TAF-ON, and TAF-OFF groups, respectively. Neither viral rebound nor CD4+decline was observed in the post-switch period in all groups. Multivariate analysis showed significant reduction in total cholesterol, LDL-C and HDL-C in the ABC-OFF group (−6.280, −6.957 and −2.268, p = 0.040, 0.012 and 0.022, respectively), but not in the TAF-OFF group (−3.000, 6.708 and 0.046, p = 0.607, 0.276 and 0.983, respectively). No significant changes were observed in body weight, eGFR, or FIB4-index at 72 weeks after the discontinuation of ABC or TAF. ConclusionsSwitching from ABC/3TC/DTG to DTG/3TC lowered lipids significantly, but not with TAF/FTC/DTG. Neither switch affected body weight or other markers.

Results from systematic review and meta-analysis of the efficacy and safety of two-drug versus three-drug ( Tenofovir/Lamivudine/Dolutegravir; TLD) regimens for HIV treatment.

Results from systematic review and meta-analysis of the efficacy and safety of two-drug versus three-drug ( Tenofovir/Lamivudine/Dolutegravir; TLD) regimens for HIV treatment.

Acceptability determinants of a proposal to reduce antiretroviral treatment to an oral two-drug regimen among patients living with HIV and physicians in France.

An oral two-drug regimen (O2DR) in the form of a once-a-day single tablet is now recommended for treatment switching and treatment initiation for HIV. In clinical care, the process of treatment change refers to adaptation issues, both individual and within the care relationship. The study aim is to present the determinants involved in the acceptability of switching to O2DR in the PROBI (Patient-Reported Outcomes BItherapy) qualitative study. The study includes 30 interviews: 15 were conducted with doctors caring for people living with HIV, 15 were conducted with patients who had been offered a change of treatment. A double analysis was carried out: lexicometric analysis to highlight the structuring of the discourse around the change in treatment and a thematic analysis to understand the associated issues more precisely. The results highlighted common concerns with respect to switching to O2DR. Also, the caregiver-patient relationship was a central determinant in treatment switching. Information, knowledge and representations of O2DR are also factors facilitating treatment change and should be taken into account for doctors' and patients' adherence.

Efficacy and safety of 2-drug regime dolutegravir/lamivudine in pregnancy and breastfeeding- clinical implications and perspectives.

To assess the efficacy and safety of a two-drug regimen (2DR) with dolutegravir (DTG) and lamivudine (3TC) in maintaining viral suppression during pregnancy and breastfeeding, and to evaluate its potential as an alternative to the recommended three-drug regimen (3DR) in preventing mother-to-child transmission (MTCT) of HIV. We present a case of a 34-year-old pregnant woman who, after discontinuing 3DR due to side effects and poor adherence, was switched to DTG/3TC at gestational week 23. Maternal viral load (VL) and infant HIV status were monitored throughout pregnancy and a ten-month breastfeeding period. Data on pharmacokinetic changes in pregnancy and the risks associated with 2DR were reviewed. The patient's VL remained suppressed (<20 copies/mL) from gestational week 23 until the end of the breastfeeding period. A healthy HIV-negative baby was born at 39 weeks, and the child remained HIV-negative after ten months of breastfeeding. The 2DR was well-tolerated, improved adherence, and reduced fetal drug exposure. Despite limited experience with 2DR in pregnancy, no viral rebound occurred, and no adverse effects were observed. Although 3DR remains the preferred therapy during pregnancy and breastfeeding, this case indicates that DTG/3TC may be an effective alternative for patients experiencing intolerance or poor adherence to 3DR. Further studies are needed to explore the impact of pharmacokinetic changes in pregnancy on 2DR efficacy and to confirm its safety and role in preventing MTCT.

Real-world data on long-acting intramuscular maintenance therapy with cabotegravir and rilpivirine mirror Phase 3 results.

Cabotegravir, an integrase strand transfer inhibitor, and rilpivirine, an NNRTI, constitute the first long-acting (LA), injectable, two-drug ART regimen approved for the maintenance of virological suppression in persons living with HIV-1 (PLHIV). The aim of this study was to assess clinical effectiveness and tolerability of LA cabotegravir/rilpivirine in a real-world setting. We conducted a retrospective, single centre study, including all PLHIV receiving LA cabotegravir/rilpivirine as standard-of-care in our tertiary centre even if initiated in clinical trials. Between 2014 and 2022, 126 PLHIV initiated LA cabotegravir/rilpivirine. All were ART-experienced, and 98.4% had a viral load (VL) of <50 copies/mL before LA cabotegravir/rilpivirine initiation. Median BMI at cabotegravir/rilpivirine initiation was 24 IQR (23-28). During a median follow-up of 9 months IQR (7-24), 27 patients discontinued cabotegravir/rilpivirine because of virological failure, 6 for adverse events, 11 for personal reasons unrelated to treatment tolerance and 5 for other reasons. Virological failure was not associated with a higher BMI, nor with weight gain during LA intramuscular (IM) cabotegravir/rilpivirine treatment, inadequate cabotegravir and rilpivirine concentrations, VL blips or the use of oral lead-in (OLI) or not. No drug resistance-associated mutation emerged. Adverse events leading to treatment interruption were injection-site pain (n = 3) and neuropsychological side effects (n = 3). A correlation between BMI and both cabotegravir and rilpivirine concentrations at 1 month post-initiation of LA-IM cabotegravir/rilpivirine was observed, with no impact of OLI. Data from this real-world cohort of PLHIV who received cabotegravir/rilpivirine LA injections suggest that this regimen is effective and well tolerated. Virological failures were not associated with the acquisition of resistance mutations.

Treatment strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for gastric cancer with peritoneal metastasis: a systematic review

Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m2 of Cisplatin and 30-40 mg/m2 of Mitomycin C in 3-4 L saline solution at 42-43℃. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.

Long term survival in adult osteosarcoma patients treated with a two-drug regimen: Final results of the OSAD93 phase II study of the FSG-GETO

RationaleWe report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. Patients and methodsThis is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. ResultsFrom Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16–63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3–4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. ConclusionThough the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.

Effectiveness and safety of dolutegravir plus lamivudine in treating HIV in China, including outcomes of patients coinfected with tuberculosis.

Antiretroviral regimens for human immunodeficiency virus (HIV) infection have continuously evolved; however, antiretrovirals can cause severe adverse reactions. Two-drug regimen therapy can decrease lifetime cumulative drug exposure and long-term toxicities associated with multiple antiretrovirals. The preferred 2-drug regimen constitutes dolutegravir (DTG) and lamivudine (3TC). This study determined the rate of virological suppression and incidence of adverse events at week 48 in treatment-naïve people living with HIV initiated on DTG + 3TC. This was a single-center, retrospective, observational study. Treatment-naïve people aged ≥18 years who received at least 1 DTG + 3TC dose between May 2020 and May 2022 were included. Eighty-nine people living with HIV were enrolled. Twenty-five (28.1%) patients with a DTG + 3TC regimen at baseline were analyzed because of comorbidities, and 48% because of concomitant tuberculosis (TB). Viral suppression at 48 weeks was achieved in 91.67% of patients, and TB was well controlled. At week 48, 84 (94.38%) patients had viral loads < 50 copies/mL, and 21 (91.31%) of the 23 participants with a baseline HIV-1-RNA level ≥ 1 × 105 copies/mL achieved virological success. Fifteen (88.23%) of the 17 participants with a baseline CD4 + cell count of <200 cells/µL achieved virological suppression. The median CD4 + cell count change from baseline was 539.5 cells/µL. No significant changes in triglycerides, low-density lipoprotein cholesterol, weight, or creatinine were observed from baseline to 48 weeks. One patient had severe insomnia at 4 weeks. Our findings support the real-world effectiveness and low metabolic impact of DTG + 3TC. Using DTG + 3TC in patients coinfected with TB and HIV has favorable therapeutic outcomes.

Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1β, IL-10, IL-18, IL-33, IL-36 and IFN-γ) have been evaluated. CD4 + cell’s median value was 729.0 cell/µL in the 3DR group and 771.5 cell/µL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/µL in 3DR group vs. 475.0 cell/µL in 2DR group, p = 0.034) and IL-36 (281.7 cell/µL in 3DR group vs. 247.0 cell/µL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1β, IL-10, IL-33, and IFN-γ levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Effect of neratinib on HER2 mRNA stability via hsa-miR-23a-5p and efficacy of CDK4/6 inhibitors in HER2-low breast cancer.

e12550 Background: Traditional HER2-negative breast cancer sometimes includes HER2-low components, and CDK4/6 inhibitors are the first- and second-line treatments for advanced HER2-low breast cancer. Nonetheless, little is understood about how the stability of HER2 mRNA in HER2-low breast cancer affects the effectiveness of CDK4/6 inhibitor therapy and the associated intervention techniques. Methods: In order to investigate the impact of HER2-low on the effectiveness of CDK4/6 inhibitor in treating breast cancer, we first used HER2-0 and HER2-low breast cancer cells/mice as the study object and assessed the anti-proliferation effect of CDK4/6 inhibitor using CCK8 technique and monoclonal formation experiment. Second, we increased the treatment of anti-HER2 inhibitor neratinib and assessed its impact on the efficacy of HER2 low breast cancer CDK4/6 inhibitors. By reducing the expression of HER2 in HER2 low breast cancer cells, we analyzed and determined whether HER2 is the primary pathway that influences the poor efficacy of HER2 low breast cancer CDK4/6 inhibitors; At last, actinomycin D was used to detect the mRNA stability of HER2 in the treatment of HER2-low breast cancer by neratinib against CDK4/6 inhibitors, and then microRNA sequencing and luciferase reporter gene detection technology were used. To investigate the specific mechanism of action of neratinib on the mRNA stability of HER2 in the treatment of HER2-low breast cancer by CDK4/6 inhibitors. Results: Our study found that treatment with CDK4/6 inhibitors was significantly less effective against HER2-low breast cancer compared to HER2-0 subtype (P=0.005). Notably, in HER2-low subtype cells, HER2 knockdown significantly inhibited cell proliferation (P&lt;0.001), G1 phase cell cycle arrest (P=0.001), and downregulated cyclin D1 expression and CDK4 protein levels (P=0.007, P=0.003). Second, it was found that in the cell and animal models of HER2-low breast cancer, the addition of the CDK4/6 inhibitor drug neratinib effectively reduced the stability of HER2 mRNA (P=0.001), inhibited the cell cycle of G1 phase (P=0.005). In addition, we observed that lowering the dose of neratinib to 1/2 (20 mg/kg) remained effective and well tolerated (P=0.002). Finally, we found that neratinib can reduce the mRNA stability of HER2 by binding hsa-miR-23a-5p to the 3'UTR region of HER2 (P&lt;0.001), thereby improving the efficacy of CDK4/6 inhibitors in HER2-low breast cancer. Conclusions: We found that low expression of HER2 reduced the efficacy of CDK4/6 inhibitors in HER2-low breast cancer; Neratinib reduces the mRNA stability of HER2 by binding hsa-miR-23a-5p to the 3 'UTR region of HER2, thereby improving the efficacy of CDK4/6 inhibitors in HER2-low breast cancer. These findings provide a tolerable and effective two-drug combination regimen for patients with clinical HER2-low breast cancer.

Comparison of checkpoint inhibitor–based regimens as first-line therapy in advanced hepatocellular carcinoma: A Frequentist Network meta-analysis of randomized clinical trials.

e16136 Background: Multiple immune checkpoint inhibitor (ICI) based regimens have shown better responses and survival rates than previously used sorafenib/lenvatinib in advanced hepatocellular carcinoma (HCC). However, there was no direct comparison done among different ICI-based regimens. This network meta-analysis focuses on the efficacy of different ICI-based regimens in advanced HCC as first-line therapy. Methods: A comprehensive literature search was performed on PubMed, and Embase from the inception of data till 12/30/2023 with keywords for “Hepatocellular carcinoma” AND “Immune Checkpoint Inhibitors”. We screened 5120 articles and included 8 randomized clinical trials (RCTs, N = 5834). “R” software and netmeta package was used to conduct this network meta-analysis. Atezolizumab + cabozantinib was randomly chosen as the comparator group. Results: 2208 patients were treated with ICI-based two-drug regimens, 1102 patients were treated with ICI monotherapy, 1937 patients were treated with sorafenib, and 399 patients were treated with lenvatinib. Overall survival (OS) was 0.63 (0.43-0.93), 0.64 (0.43-0.98), and 0.69 (0.48-0.99) in favor of sintilimab + bevacizumab, atezolizumab + bevacizumab, and camrelizumab + rivoceranib, respectively, as compared to atezolizumab + cabozantinib. Progression free survival (PFS) was 0.83 (0.54-1.27), 0.89 (0.58-1.35), and 0.94 (0.61-1.45) in favor of camrelizumab + rivoceranib, sintilimab + bevacizumab, and atezolizumab + bevacizumab, respectively, as compared to atezolizumab + cabozentinib. Odds ratio of overall response rate (ORR) 2.03 (0.67-6.13), 1.7 (0.65-4.43), and 1.46 (0.58-3.67) in favor of sintilimab + bevacizumab, camrelizumab + rivoceranib, and tremlimumab + durvalumab, respectively, as compared to atezolizumab + cabozantinib. P-scores for each regimen are in Table. Conclusions: Among ICI combinations, better survival and response rates were reported with sintilimab + bevacizumab, atezolizumab + bevacizumab, and camrelizumab + rivoceranib. Therefore, these regimens should be preferred for treatment of advanced HCC as first line therapy in patients who can tolerate these regimens. [Table: see text]

Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial

Doravirine and islatravir is an investigational, once-daily, single-tablet regimen with high antiviral potency, favourable safety and tolerability, and low propensity for resistance. We report week 48 results from a phase 3 trial evaluating switch from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (0·75 mg). This phase 3, multicentre, randomised, active-controlled, open-label, non-inferiority trial was conducted at 77 research, community, and hospital-based clinics in 15 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL on any oral, two-drug or three-drug ART regimen for at least 3 months, and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation schedule to switch to doravirine (100 mg) and islatravir (0·75 mg) or to continue their baseline ART regimen. Block randomisation was based on a block size of four, and randomisation was stratified by baseline regimen (ie, protease inhibitor, integrase inhibitor, or other). Participants in the doravirine and islatravir group were instructed to take one tablet at approximately the same time each day, and participants in the baseline ART group continued to take the medication according to the locally approved label. HIV-1 RNA and safety evaluations were done at baseline and weeks 4, 12, 24, 36, and 48. CD4 cell counts were measured at baseline, week 24, and week 48. The primary endpoint was proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug) using the US Food and Drug Administration snapshot approach and prespecified non-inferiority margin of 4%. This study is registered with ClinicalTrials.gov (NCT04223778) and is completed. Between Feb 18 and Oct 2, 2020, 740 individuals were screened for eligibility, of whom 672 (90·8%) participants (249 [37·1%] women and 423 [62·9%] men; median CD4 count of 678 cells per μL [IQR 496-868]) were randomly assigned to doravirine (100 mg) and islatravir (0·75 mg; n=336) or to continue baseline ART (n=336). The last follow-up visit occurred on Sept 8, 2021. At week 48, zero of 336 participants in the doravirine and islatravir group versus five (1·5%) of 336 participants in the baseline ART group had greater than or equal to 50 HIV-1 RNA copies per mL (difference -1·5, 95% CI -3·4 to -0·3). The per-protocol analysis showed consistent results. Headache was the most common adverse event in both groups (35 [10·4%] of 336 participants in the doravirine and islatravir group, 16 [4·8%] of 336 in the baseline ART group), infection rates were similar (113 [33·6%] in both groups), and discontinuations due to adverse events were low (seven [2·1%] vs one [0·3%]). 66 (19·6%) of 336 participants had treatment-related adverse events in the doravirine and islatravir group compared with 30 (8·9%) of 336 in the baseline ART group. In the islatravir and doravirine group, CD4 cell counts (mean change -30·3 cells per μL) and total lymphocyte counts (mean change -0·26 × 109/L) were decreased at 48 weeks. Switching to single-tablet doravirine (100 mg) and islatravir (0·75 mg) maintained viral suppression up to week 48 and was non-inferior to antiretroviral combinations used in clinical practice for adults with HIV-1; however, decreases in CD4 cell and total lymphocyte counts do not support further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). Merck Sharp & Dohme, a subsidiary of Merck & Co.

D3/Penta 21 clinical trial design: A randomised non-inferiority trial with nested drug licensing substudy to assess dolutegravir and lamivudine fixed dose formulations for the maintenance of virological suppression in children with HIV-1 infection, aged 2 to 15 years

BackgroundThere is increasing interest in utilising two-drug regimens for HIV treatment with the goal of reducing toxicity and improve acceptability. The D3 trial evaluates the efficacy and safety of DTG/3TC in children and adolescents and includes a nested pharmacokinetics(PK) substudy for paediatric drug licensing. MethodsD3 is an ongoing open-label, phase III, 96-week non-inferiority randomised controlled trial(RCT) conducted in South Africa, Spain, Thailand, Uganda and the United Kingdom. D3 has enrolled 386 children aged 2- < 15 years, virologically suppressed for ≥6 months, with no prior treatment failure. Participants were randomised 1:1 to receive DTG/3TC or DTG plus two nucleoside reverse transcriptase inhibitors(NRTIs), stratified by region, age (2- < 6, 6- < 12, 12- < 15 years) and DTG use at enrolment (participants permitted to start DTG at enrolment). The primary outcome is confirmed HIV-1 RNA viral rebound ≥50 copies/mL by 96-weeks. The trial employs the Smooth Away From Expected(SAFE) non-inferiority frontier, which specifies the non-inferiority margin and significance level based on the observed event risk in the control arm. The nested PK substudy evaluates WHO weight-band-aligned dosing in the DTG/3TC arm. DiscussionD3 is the first comparative trial evaluating DTG/3TC in children and adolescents. Implications of integrating a PK substudy and supplying data for prompt regulatory submission, were carefully considered to ensure the integrity of the ongoing trial. The trial uses an innovative non-inferiority frontier for the primary analysis to allow for a lower-than-expected confirmed viral rebound risk in the control arm, while ensuring interpretability of results and maintaining the planned sample size in an already funded trial. Trial registrationInternational Standard Randomised Clinical Trial Number Register: ISRCTN17157458.European Clinical Trials Database: 2020–001426-57.ClinicalTrials.gov: NCT04337450

Survey on the Use of Medicines in Patients with Co-existing Hypertension and Type 2 Diabetes at the Internal Medicine Department of E Hospital in 2020-2022

The study aims to describe the situation of using antihypertensive and hypoglycemic drugs; Initial evaluation of the effectiveness of drug used in the treatment regimen of patients with concomitant hypertension and type 2 diabetes. Methods: a cross-sectional, retrospective study was performed on 179 medical records of patients who had hypertension and type 2 diabetes, examination and treatment at the Internal Medicine Department - Hospital E from April 2020 to December 2022. Information collected from medical records was processed using SPSS 26.0 statistical software. Result: the main groups of hypoglycemic drugs used were metformin (74.9%) and insulin (69,3%). The rate of using multi-drug regimen for diabetes (64.8%) is higher than that of monotherapy, in which the two-drug regimen of insulin and biguanide (metformin) is common (32.4%). The main groups of antihypertensive drugs used were ACE inhibitors and Ca channel blockers (72.6% and 57.5%), 60.3% of patients were treated according to a multi-drug regimen in which combination regimens of 2 groups of Ca channel blockers and ACE inhibitors are common (26.3%). There are no clinically significant interactions between antidiabetic and antihypertensive drugs. The rate of patients who reached the target blood pressure was 83.8%. The rate of patients achieving target blood sugar levels when discharged from the hospital was 40.9%. Conclusion: multi-drug regimen is used more than monotherapy in the treatment of hypertension and diabetes. Most patients reached target blood pressure on discharge, however the number of patients achieving target blood glucose was quite limited . No drug interactions were found between drugs used to lower blood pressure and hypoglycemic drugs.&#x0D;

Two-Drug Regimens Dolutegravir/Lamivudine and Dolutegravir/Rilpivirine Are Effective with Few Discontinuations in US Real-World Settings: Results from the TANDEM Study.

Dolutegravir/lamivudine (DTG/3TC) and dolutegravir/rilpivirine (DTG/RPV) are fixed-dose, complete, single-tablet, two-drug regimens (2DRs) indicated for HIV-1. DTG/3TC is approved for antiretroviral therapy (ART)-naive people with HIV-1 and virologically suppressed individuals to replace current ART; DTG/RPV is indicated for virologically suppressed individuals as a switch option. Virologic efficacy and effectiveness of these DTG-based 2DRs have been demonstrated in phase3 clinical trials and real-world cohorts, primarily from Europe. This study characterized real-world use of DTG-based 2DRs for HIV-1 treatment in the USA. TANDEM was a retrospective medical chart review across 24 US sites. Individuals aged ≥ 18years who initiated DTG/3TC or DTG/RPV before September 30, 2020, with ≥ 6months of follow-up were included. One cohort included ART-naive people who initiated DTG/3TC (n = 126), and two other cohorts included virologically suppressed (HIV-1 RNA < 50 copies/mL) people on stable ART regimens for ≥ 3months before switch to either DTG/3TC (n = 192) or DTG/RPV (n = 151). Clinical characteristics, treatment history, and outcomes are described. Virologically suppressed individuals were older than those who were ART-naive, and the ART-naive cohort had higher proportions of individuals assigned male at birth and of Hispanic ethnicity. The most common healthcare provider-reported reason for choosing a DTG-based 2DR was avoidance of long-term toxicities (25-33% across cohorts), followed by simplification/streamlining of treatment. Among ART-naive people on DTG/3TC, 94% achieved virologic suppression after initiation, and 83% maintained suppression at last follow-up; discontinuation rate was < 1%. Among cohorts who switched to DTG-based 2DRs, 96% maintained virologic suppression on DTG/3TC and 93% on DTG/RPV; 2% on DTG/3TC and 3% on DTG/RPV discontinued. Motivation for selecting DTG-based 2DRs was primarily driven by a desire to avoid or manage toxicities and simplify treatment. Results demonstrate that DTG/3TC and DTG/RPV are effective in real-world settings, with few discontinuations, reflecting data from clinical trials.

Switching to Dolutegravir/Lamivudine Two-Drug Regimen: Durability and Virologic Outcomes by Age, Sex, and Race in Routine US Clinical Care.

Two-drug regimens (2DR) may address drug-drug interactions and toxicity concerns. Dolutegravir/lamivudine (DTG/3TC) 2DR was approved in the US for both treatment-naïve and treatment-experienced individuals with a viral load <50 copies/mL. This study describes real-world DTG/3TC 2DR treatment outcomes among treatment-experienced individuals, stratified by age, sex, and race. From the OPERA® cohort, people with HIV with a viral load <50 copies/mL who switched from a commonly used three-drug regimen to DTG/3TC 2DR as per the label between April 8, 2019 and April 30, 2021 were included. Incidence rates (Poisson regression) for loss of virologic control (first viral load ≥50 copies/mL), confirmed virologic failure (2 viral loads ≥200 copies/mL or discontinuation after 1 viral load ≥200 copies/mL), and DTG/3TC 2DR discontinuation were estimated overall and stratified by age, sex, and race. The 787 individuals included were followed for a median of 13.6 months (IQR: 8.2, 22.3). Confirmed virologic failure occurred in ≤5 individuals. Loss of virologic control occurred at a rate of 14.0 per 100 person-years (95% CI: 11.7, 16.8). DTG/3TC 2DR discontinuation occurred at a rate of 17.5 per 100 person-years (95% CI: 15.0, 20.3); 4% discontinued for treatment-related reasons (viremia, adverse diagnosis, side effect, lab abnormality). For all outcomes, incidence rates were comparable across strata of age, sex, and race. This descriptive study demonstrates that DTG/3TC 2DR is an effective and well-tolerated treatment option for people with HIV with a viral load <50 copies/mL at switch, regardless of their age, sex, or race.

Elderly Patients with Newly Diagnosed Multiple Myeloma: Continuous or Fixed Duration Treatment?

Multiple myeloma (MM) presents unique challenges in the elderly population due to increased frailty and comorbidities. Balancing treatment efficacy, safety, and quality of life is essential in managing elderly patients. While two-drug regimens were often favored for elderly patients, recent studies show promising outcomes with anti-CD38 antibody-based therapies, particularly daratumumab and lenalidomide with minimal dexamethasone. Continuous low-intensity treatments have shown improved progression-free survival and overall survival, with significant benefits observed in elderly patients. The DRd combination has now emerged as the standard of care for elderly MM patients, offering a favorable balance of efficacy, safety, and convenience. Ongoing trials are evaluating the addition of bortezomib in an induction phase for fit patients. New-generation immunotherapies hold promise for further refining treatment approaches, potentially leading to treatment discontinuation in select patient populations with sustained minimal residual disease negativity.