Lines Of Treatment Research Articles

Clinical significance of complete remission and measurable residual disease in relapsed/refractory multiple myeloma patients treated with T-cell redirecting immunotherapy.

The impact of measurable residual disease (MRD) in relapse/refractory multiple myeloma (RRMM) patients treated with T-cell redirecting immunotherapy is uncertain. We analyzed MRD dynamics using next-generation flow in 201 patients treated in clinical trials with chimeric antigen receptor (CAR) T cells and T-cell engagers (TCE). Achieving MRD negativity at 10-6 was associated with 89% reduction in the risk of progression and/or death. Survival outcomes were improved in patients with sustained versus transient MRD negativity and were dismal in those who remained MRD positive. The intent-to-treat MRD negative rates were higher in patients treated with CAR T cells versus TCE. However, among patients achieving MRD negativity, there were no differences in survival outcomes when stratified according to treatment with CAR T cells versus TCE. In multivariate analysis including the number of prior lines of treatment, International Staging System, cytogenetic risk, extramedullary disease and type of T-cell redirecting immunotherapy, only the complete remission (CR) and MRD statuses showed independent prognostic value for progression-free and overall survival. In conclusion, our study shows that deep and sustained MRD negative CR is the most relevant prognostic factor and should be considered as the treatment endpoint in RRMM patients treated with CAR T cells and TCE.

Real-world outcomes of everolimus-based treatment in a Taiwanese cohort with metastatic HR+/HER2- breast cancer.

Everolimus was the first orally targeted therapy for certain cancers. It was introduced before CDK4/6 inhibitors and is widely used to treat advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This study presents comprehensive findings including updated data and long-term survival analyses focusing on patients with HR+/HER2- metastatic breast cancer who received everolimus-based treatment. The objectives were to assess the impact of everolimus on overall survival (OS) and progression-free survival (PFS) by treatment line, and to evaluate its role in therapeutic strategies in a real-world setting. We included 299 women aged over 20 years with histologically confirmed HR+/HER2- breast cancer who received everolimus-based treatment from multiple medical centers in Taiwan. Survival curves were generated using the Kaplan-Meier method, with the log-rank test for comparisons. Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events version 5.0. The median PFS was 5.6 months, and the median OS was 60.1 months. Patients receiving everolimus treatment in three or more lines and those who underwent chemotherapy prior to everolimus-based treatment had a significantly shorter PFS but longer OS. Patients with liver and central nervous system metastases had significantly shorter PFS and OS. The disease control rate was 51.5%, and the overall response rate was 8.0%. These findings support current guidelines and advocate for the inclusion of everolimus in treatment plans for patients with metastatic HR+/HER2- breast cancer, particularly in late-line treatment, with careful consideration of the benefit-risk profile for each patient.

CTIM-22. MEDIAN AND 2 YEARS SURVIVAL OF NEWLY DIAGNOSED UNMETHYLATED MGMT GLIOBLASTOMA PATIENTS TREATED WITH TEMFERON IMMUNO-GENE THERAPY

Abstract TEM-GBM is an open-label, Phase 1/2a dose-escalation study aimed to evaluate the safety and efficacy of a myeloid cell-targeted therapy (Temferon) in up to 27 newly diagnosed GBM patients with unmethylated MGMT (uMGMT). Temferon, consists of autologous Hematopoietic Stem Progenitor Cells (HSPCs) genetically modified with a lentiviral vector to deliver IFN-α2 within the tumor microenvironment by Tie-2 expressing macrophages. As of 21st May 2024, 24 GBM patients in 8 cohorts received incremental doses of Temferon and 6 are still alive. For all patients, median overall survival (OS) and median progression free survival reach 17 months and 8.3 months from first surgery, respectively. The interim survival rate at 2 years in Temferon-treated patients is 30% (6 of 20 patients; 3 patients excluded as follow-up is below 1 year). The mOS and the % of patients surviving up to 2 years are currently higher than previously reported for uMGMT patients treated as per standard practice (12.7 months and 14,8%, respectively). Two out of the six patients did not receive any additional treatment lines up to two years after 1st surgery. The other four patients instead received a 2nd treatment line (bevacizumab, regorafenib, Gamma-Knife, metronomic Temozolomide, Lomustine) as per the PI judgment, on average after 443 days from 1st surgery (333 days from Temefron - range 223-1030 days from first surgery). Specifically, Bevacizumab administration started 12 months after 1st surgery for one patient and 19 months for the other 2 patients at 5 mg/kg. The data further confirms the initial evidence on safety and tolerability of Temferon and highlight the potential to prolong the survival of patients affected by uMGMT GBM.

Comparison of efficacy and safety of regorafenib and anti-EGFR targeted therapy in metastatic colorectal cancer: A retrospective study

Aim. To compare the efficacy of regorafenib and the combination of chemotherapy (CT) with anti-EGFR (cetuximab/panitumumab) in the third-line treatment of metastatic colorectal cancer (mCRC). Materials and methods. A retrospective analysis of a prospective database of patients with mCRC from two clinics in the Russian Federation was conducted. Overall survival was considered the primary efficacy criterion. Additional criteria were progression-free survival (PFS), objective effect (OE), and incidence of toxicity. No statistical hypothesis was assumed. Statistical analysis was performed using SPSS (IBM SPPS Statistics v. 20). Results. The database identified 51 patients with morphologically confirmed left-sided mCRC with wild-type RAS and BRAF genes who received more than two lines of antitumor drug therapy from 2010 to 2021, one of which included anti-EGFR antibodies in the third and subsequent lines of treatment. Thirty patients who received regorafenib in the third line and 21 patients who received CT in combination with anti-EGFR in the third line were selected, of which 7 patients had a history of anti-EGFR use, and 14 patients received anti-EGFR for the first time. The median overall survival from the third line initiation date in the CT group in combination with anti-EGFR was numerically higher (21 months, CI 9.0–32.9 months) than in the regorafenib group (10 months, CI 2.4–17.5 months); p=0.1 by log-rank test (Mantel–Cox test); p=0.2 by Breslow–Wilcoxon test; p=0.3 (Tarone–Ware test). PFS was also higher in the anti-EGFR CT group (6 months, CI 3.8–8.2 months) than in the regorafenib group (3 months, CI 1.2–4.7 months); p=0.05 according to Breslow–Wilcoxon test. OE of third-line therapy was reported in 57.1% (n=12) of patients in the CT with anti-EGFR group and significantly less often in the regorafenib group – 10.3% (n=3) of patients (p=0.001). The toxicity of drug therapy of all grades in the regorafenib group was reported in 86.2% (n=25) of patients, while in the CT anti-EGFR group, it was significantly less common – in 52.4% (n=11) of patients (p=0.01). Conclusion. Compared with regorafenib, combining CT with anti-EGFR agents in the third-line treatment of patients with left-sided mCRC with wild-type RAS and BRAF genes is associated with better PFS and the frequency of OE with significantly less toxicity.

Olaparib-induced myelodysplasia – A case report

Olaparib is an antineoplastic agent that is a poly ADP ribose polymerase (PARP) inhibitor and is Food and Drug Administration-approved for the treatment of ovarian, breast, pancreatic, and prostate cancer. PARP inhibitors can cause DNA damage and epigenetic changes, leading to hematological transformations and increasing the risk of myelodysplasia. We present a case of a 58-year-old female with malignant breast cancer initiated on Olaparib after failing multiple treatment lines. The patient had persistent declining blood cell counts, and a bone marrow biopsy revealed hypercellular bone marrow with predominant myeloid cells with increasing number of blasts and promyelocytes. Olaparib was stopped. The patient elected for supportive care and hospice.

New therapies for hormone-positive HER2-negative metastatic breast cancer with AKT signaling alterations: the Expert Panel Decision

On May 20, 2024, the Expert Panel discussed key issues of the diagnosis of alterations of the AKT signaling pathway, the effectiveness and safety of targeted therapy for hormone-positive (HR+) HER2-negative metastatic breast cancer (BC) concerning the emergence of a new selective AKT inhibitor capivasertib. The results of the CAPItello-291 study are presented. The experts concluded that a new effective treatment line has become available for patients with hormone-resistant advanced hormone-positive HER2-negative BC with genetic alterations in the AKT signaling pathway and relapse on previous adjuvant endocrine therapy with aromatase inhibitors or within the first year after the therapy or with progression during previous therapy with aromatase inhibitors for metastatic BC. Modern genetic testing methods for the alterations in the AKT signaling pathway can confirm the presence of this key biological target in the tumor for tailoring effective targeted therapy.

Overall survival of patients with KIT-mutant metastatic GIST in the era of multiple kinase inhibitor availability

PurposeThe prognosis of patients with metastatic GIST and imatinib-sensitive primary mutations has significantly improved. However, limited data are available to inform patients about outcomes across different lines of treatment. This retrospective analysis aims to evaluate patient outcomes at a large German GIST referral center over the past 15 years.Patients and methodsOverall survival (OS) and progression-free survival (PFS) were analyzed in patients with metastatic GIST, with diagnosis of metastases between 2008 and 2021, when at least three lines of treatment were available in Germany (n = 174).ResultsThe median overall survival far exceeds historical data for patients with primary exon 11 and exon 9 mutations (median OS in palliative treatment with imatinib: 7.1 years; median OS in second-line palliative treatment with sunitinib: 2.9 years; median OS in third-line palliative treatment with regorafenib: 1.9 years). Among those patients who received palliative imatinib treatment, no significant difference in median OS survival was observed between those who had received perioperative imatinib for localized disease and those who did not. Furthermore, the location of metastases significantly impacted survival, whereas the time between the initial diagnosis and the diagnosis of metastases had no significant effect on survival.ConclusionIn conclusion, this study provides a novel, real-world reference for survival outcomes in patients with metastatic GIST.

An Atypical Case of Pancreatic Cancer with Mesenchymal Differentiation in a Patient with Primary Lung Adenocarcinoma: Insights into Tumor Biology and Novel Therapeutic Pathways

Background: Pancreatic cancer is among the malignancies with the poorest prognosis, largely due to its aggressive nature and resistance to conventional therapies. Case Summary: This report describes the case of a 69-year-old male patient with stage IV primary lung adenocarcinoma presenting with high levels of programmed death-ligand 1 (PD-L1). Simultaneously, abdominal computed tomography (CT) showed a dilated pancreatic duct at the level of the pancreatic head and a hypodense lesion in the uncinate process involving the superior mesenteric artery. Fine-needle aspiration (FNA) of the pancreatic lesions was negative. After three cycles of chemoimmunotherapy, positron emission tomography–computed tomography (PET-CT) showed complete remission of the lung nodules, lymphadenopathy, and pleural thickening, as well as a decrease in the size of the pancreatic lesion. After another six months, a PET-CT scan showed a focal increased uptake in the pancreatic mass in the same location, indicating disease progression. A core biopsy of the pancreatic tumor showed atypical spindle cell morphology with positive staining for vimentin, characteristic of mesenchymal differentiation with no apparent epithelial features. Comprehensive molecular profiling through Caris Molecular Intelligence® revealed four genes with actionable mutations in the pancreatic tissue, including KRAS (p.G12D) and TP53 (p.R175H). These molecular findings suggested the diagnoses of sarcomatoid carcinoma and conventional pancreatic ductal adenocarcinoma with epithelial–mesenchymal transition. Primary mesenchymal tumors and neuroendocrine neoplasms were excluded because immunohistochemistry was negative for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA), desmin, CD34, signal transducer and activator of transcription 6 (STAT6), S100, HMB45, CD117, discovered on GIST-1 (DOG1), CD56, progesterone, and synaptophysin. However, despite multiple rounds of systemic chemotherapy, immunotherapy, and radiation, his pancreatic disease rapidly deteriorated and metastasized to the liver and bone. Conclusions: Despite multiple lines of treatment, the patient’s condition worsened and he succumbed to his pancreatic malignancy. This study highlights the clinical characteristics, diagnosis, and treatment of rare pancreatic cancer, emphasizing the importance of molecular testing and histopathological biomarkers in personalizing treatment. It also provides insights into promising therapeutic approaches for similar cases with an unusual presentation.

Time from Final Oncologist Visit to Death and Palliative Systemic Treatment Use Near the End of Life in Heavily Pretreated Patients with Luminal Breast Cancer

Background: Palliative care must be tailored for patients with extended disease trajectories, such as those with hormone receptor-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer (ABC), including the appropriate timing of discontinuing treatment. This study aimed to assess the interval between the last oncologist visit and death and the application of systemic treatment near the end of life in this patient population. Methods: This retrospective study included patients with luminal ABC who received at least two lines of palliative systemic treatment at the National Research Institute of Oncology in Poland, and died between November 2020 and March 2024. Results: Seventy-six women, with a median age 62.8 years (range: 35.3–91.5), were included. The median number of prior palliative systemic treatment lines was three (range: 2–6). At their last recorded oncologist visit, 75% of the patients were receiving active treatment (53% with hormonal therapy and 22% with chemotherapy). Only 25% were under continuous palliative care at this visit. Treatment was administered within the last month of life to 53% of the patients. The median duration from the last oncologist visit to death was 23 days (range: 0–408). The duration of this time interval was only associated with the performance status at the last visit (p < 0.05). Conclusions: Oncologists frequently delay the recognition of the need to discontinue systemic therapy. Patients with luminal HER2-negative ABC may be offered numerous effective lines of systemic treatment, complicating this decision further. Implementing clearer guidelines for end-of-life care for this group and providing proper training for healthcare providers is essential.

The Efficacy of a Lower Dose of Everolimus in Patients with Advanced Neuroendocrine Tumors

Background: Everolimus at 10 mg daily is approved to treat patients with advanced grade 1/2 neuroendocrine tumors (NETs), although it may lead to significant toxicity. Grade 3 or higher drug-related adverse events and drug discontinuation occur in approximately one-fourth of cases. However, phase I trials have demonstrated that doses from 5 mg daily efficiently inhibit NET cell signaling. Objectives and Methods: This multicenter retrospective study compared the time to treatment failure (TTF) in patients with NETs who received a mean daily dose of 7–10 mg (higher dose [HD]) or ≤6 mg (lower dose [LD]) of everolimus. Results: Ninety-two patients were included: 74 (80%) in the HD group and 18 (20%) in the LD group. At a median follow-up of 4.2 years, the median time to treatment failure (TTF) was 9.2 months for the HD and 7.2 months for the LD groups (p = 0.85). The TTF did not significantly differ between the LD and the HD groups (HR: 1.24; 95% CI: 0.68–2.25; p = 0.47), even after adjusting for age at treatment initiation, the NET grade, and the treatment line. Conclusion: Everolimus doses from 5 to 6 mg/day seem to be equally as effective as higher doses, but lower doses are potentially associated with less toxicity and lower costs. These findings support validation through a randomized clinical trial.

High BRAF V600 Mutation Level Associated with Worse Outcome in Metastatic Melanoma Patients Receiving BRAF and MEK Inhibitors.

The prognostic value of BRAF V600 mutation level on clinical outcomes in patients with BRAF V600-mutated metastatic melanoma treated with BRAF and MEK inhibitors remains uncertain. The association was retrospectively analysed between BRAF V600 mutation level (defined as the ratio of the quantification of the BRAF V600 allele to the percentage of tumoral cells in the sample analysed) and progression-free and overall survival (PFS and OS, respectively) and 3-month response rate in a cohort of 58 patients with metastatic melanoma who harboured BRAF V600E/K mutations and received dual targeted-therapy BRAF/MEK inhibitors. The BRAF mutation level cut-off determined by the area under the receiver operating characteristic curve after internal validation by bootstrap methods was 0.44. Risk of poor PFS and OS was associated with BRAF V600 mutation level > 0.44 on multivariate analysis (p = 0.02 and p = 0.02, respectively) after adjusting for major confounding factors (age, sex, lactate dehydrogenase level, brain metastasis, and treatment line). No association was found between BRAF mutation level and 3-month response rate. Our study shows that high BRAF V600 mutation level in melanoma tissue was associated with poor prognosis in patients with metastatic melanoma treated with BRAF and MEK inhibitors.

Treatment sequences and survival outcomes in advanced HR + HER2- breast cancer patients: a real-world cohort.

Palliative treatment options for HR + HER2- advanced breast cancer (ABC) patients have increased, but data is lacking about the optimal treatment sequence. We used real-world data from a comprehensive cancer center to describe applied treatment sequences and we determined treatment-related and survival outcomes. Patients aged 18 years and older with HR + HER2- ABC treated with systemic treatment were included in this historic cohort study. Sequential treatment schedules, time to treatment discontinuation, time to chemotherapy, and overall survival (OS) were determined, stratified by first-line treatment. 202 patients were included. They received a total of 650 treatment lines (median 3; range: 1-11). 91 (45%), 25 (12%), 24 (12%), 28 (14%), 22 (11%) and 12 (6%) patients started first-line treatment with non-steroidal aromatase inhibitors (NSAI), NSAI + cyclin dependent kinase 4/6-inhibitors (CDK4/6i), fulvestrant + CDK4/6i, tamoxifen, chemotherapy and other treatment, respectively. 10, 13, and 14 different treatment regimens were given in first, second and third-line, respectively. Of the patients who started first-line NSAI monotherapy (n = 91), 3 (3%) died before receiving second-line treatment. In this real-world cohort, we observed a wide variety of different treatment sequences applied in daily clinical practice, some of which were in discordance with the current guidelines. Fear that patients may never get around to treatment with CDK4/6i if a patient did not start with a CDK4/6i was not supported by our study results.

Stromal tumor infiltrating lymphocytes in hormone receptor positive/HER2 negative metastatic breast cancer

The immune landscape of hormone receptor positive, HER2-negative metastatic breast cancer (HR+/HER2- mBC), the most common subtype of BC, remains understudied. This is mainly due to reduced sample acquisition opportunities from metastases as compared to primary tumors. In this study, we explored stromal tumor-infiltrating lymphocytes (sTIL) in metastatic samples collected through our post-mortem tissue donation program UPTIDER (NCT04531696). sTIL were scored as a continuous parameter according to international guidelines on 427 metastases and 38 primary untreated tumors acquired from 20 patients with HR+/HER2- mBC. ER-status was evaluated on 362 metastases with a cut-off for positivity set at 1% according to ASCO/CAP guidelines. Our analyses show that 54% and 15% of metastases had sTIL levels >1% and >5% respectively. sTIL levels tended to be lower in metastases as compared to their respective primary tumor (Estimate: -2.83, 95%CI: -5.77-0.11, p:0.07). sTIL levels were lower in metastases from invasive lobular carcinoma than in metastases from invasive breast carcinoma of no special type (Estimate: -1.67, 95%CI: -2.35--0.98, p:<0.001). A loss of ER expression was observed in 14% of all metastases, yet a negative ER-status was not significantly associated with increased sTIL levels. Finally, sTIL levels were significantly higher in lung and axillary lymph node metastases compared to all metastases. While these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provides novel and valuable insights into the state of immune infiltration in patients with metastatic HR+/HER2- BC.

NOVEL DRUG COMBINATIONS AND DONOR LYMPHOCYTE INFUSIONS ALLOW PROLONGED DISEASE CONTROL IN MULTIPLE MYELOMA PATIENTS RELAPSING AFTER ALLOGENEIC TRANSPLANT: New treatments for Multiple Myeloma patients relapsing after Allo transplant

BackgroundEven if allogeneic stem cell transplantation (allo-SCT) is curative for a minority of patients with multiple myeloma (MM), the patients who have relapsed after allo-SCT can experience long-term survival, suggesting a synergy between anti-myeloma drugs administered after allo-SCT and donor T cells. ObjectivesWe retrospectively evaluated the outcome of MM patients reported to the “Gruppo Italiano Trapianto Midollo Osseo e Terapia Cellulare” (GITMO) network, who underwent allo-SCTs between 2009 and 2018 in order to identify predictors for long-term outcome in the whole population (242 patients) and for prolonged overall survival (OS) after relapse in the subgroup of relapsed patients (118 patients). ResultsAt a median follow-up of 40.9 months after allo-SCT median OS and progression free survival (PFS) of the whole population were respectively 39.4 and 19.0 months from allo-SCT. The cumulative incidence (CI) of non-relapse mortality (NRM) was 10.3 % at one year and 27.6% at five years. Grade 2-4 acute GVHD CI was 19.8% and 5-year CI of moderate or severe chronic GVHD was 31.8%. In the multivariate model older age at transplant (p=0.020), treatment with more than 2 lines of therapy before allo-SCT (p=0.003) and transplant from unrelated or haploidentical donor (p=0.025) were significant factors associated with reduced OS. Relapse after allo-SCT occurred in 118 (59%) patients at a median of 14.3 months (IQR 7.2-26.9). Twenty (17%) received only steroids, radiotherapy or supportive care, 41 (35%) received 1 line, 23 (19%) 2 lines and 34 patients (29%) 3 or 4 lines of salvage treatment. Nine patients were exclusively treated with chemotherapy, 9 received at least one salvage treatment including immunomodulating agents (Imids), 43 patients were treated with at least one rescue therapy including proteasome inhibitors (PIs) and 37 patients received at least one salvage treatment including monoclonal antibodies (33 daratumumab, 1 elotuzumab, 1 isatuximab, 2 belantamab). Median OS of relapsed patients was 38.5 months from allo-SCT and 20.2 months from relapse. In multivariate analysis, OS after relapse was significantly prolonged in patients with a longer time to relapse after allo-SCT (time to relapse 6-24 months p=0.016; time to relapse ≥ 24 months p< 0.001) and in those who had received at least 3 salvage treatment lines (p<0.036) and donor lymphocyte infusions (DLI) (p=0.020). ConclusionsIn our study, patients transplanted in early phases of disease and with HLA identical sibling donors had the best chance of long-term survival. Late relapse after allo-SCT, multiple courses of salvage treatment and the association with DLI could allow long disease control in patients who experienced relapse after allo-SCT.

Health-care utilisation and associated economic burden in Major Depressive Disorder and Treatment-Resistant Depression in a longitudinal population-based cohort study of 110.000 patients

Major depressive disorder (MDD), and particularly treatment-resistant depression (TRD), lead to high levels of health-care use and disease burden. The aim of this study was to evaluate and compare the health-care resource utilisation and associated costs in these patient groups. It was a population-wide, retrospective analysis of NHS health-care electronic records in northwest London using the Discover-NOW platform, one of the largest interlinked datasets in Europe hosted by Imperial College Health Partners, which contains coded emergency and routine, primary and secondary, physical and mental health data, covering a population of more than 2.5 million. Eligible patients were adults with a diagnosis of MDD who had been prescribed at least one antidepressant between 2015 and 2020. A total of 110,406 patients were included, 101,333 [92%] with MDD and 9,073 [8%] with TRD. Mean duration of depression was 52.8 (SD 41.7) months for MDD and 70.8 (SD 37.8) months for TRD (p<0.0001). Patients with TRD had significantly higher risks of both psychiatric and somatic comorbidities such as anxiety, asthma, and alcohol misuse (all p<0.0001). They also demonstrated increased primary care and emergency attendance rates, more frequent and longer hospitalizations, and on average 1.5 times greater total healthcare costs compared to MDD patients. Primary care visits represented the largest proportion overall (TRD mean 162 [SD 96] vs. MDD 108 [90] visits per patient, p<0.0001; cost per patient £17,348 [SD £33,040] vs. £12,011 [£25,588], p<0.0001) during the study period. In secondary care, accident and emergency visits accounted for the highest use (TRD mean 5.5 [10.6] vs. MDD 3.54 [SD 6.0] visits per patient, p<0.0001) while non-elective hospitalisations incurred the highest costs (mean £2,518 [£8,064] vs. £1,909 [SD £6,807], p<0.0001). Demand increased with the duration of depression and the number of lines of treatment. The study highlights the substantial clinical and economic burden associated with MDD and especially TRD across different care settings.

The Efficacy and Safety of Trastuzumab in the Metastatic Breast Cancer.

The aim of this study was to explore the efficacy and safety of Trastuzumab-Deruxtecan (T-DXd) in metastatic breast cancer (mBC). This retrospective observational study was conducted between January 2021 and 2023. Patients' clinical and pathological characteristics and previous medicinal treatments were reviewed. The efficacy of T-DXd and its influencing factors, as well as the adverse reactions of T-DXd were also observed. The median age of the patients was 43 years, and the median number of treatment lines was 4. In the overall population, the objective response rate (ORR) was 72.7%, the disease control rate (DCR) was 90.9%, and the median progression-free survival (mPFS) was six months. Among them, two patients temporarily discontinued treatment after two cycles of T-DXd due to financial reasons, but their disease remained stable for 5 and 8 months, respectively. Efficacy was better in patients with HER-2 amplification, who had not previously used antibody drug conjugates (ADC) drugs, were sensitive to anti-HER-2 treatment, and had ≤3 lines of therapy. Common adverse reactions during T-DXd treatment included gastrointestinal reactions such as nausea, vomiting, diarrhoea, and constipation, as well as haematological toxicities, decreased appetite, hair loss, and fatigue. Some patients experienced gastritis, abnormal liver function, and weight gain, but none of the patients developed interstitial pneumonia. T-DXd can achieve significant and durable survival benefits with controllable safety in patients with HER2-positive or HER2 low-expressing mBC. Key Words: Metastatic breast cancer, Trastuzumab-Deruxtecan, Efficacy, Safety.

The Efficacy and Safety of Trastuzumab in the Metastatic Breast Cancer.

The aim of this study was to explore the efficacy and safety of Trastuzumab-Deruxtecan (T-DXd) in metastatic breast cancer (mBC). This retrospective observational study was conducted between January 2021 and 2023. Patients' clinical and pathological characteristics and previous medicinal treatments were reviewed. The efficacy of T-DXd and its influencing factors, as well as the adverse reactions of T-DXd were also observed. The median age of the patients was 43 years, and the median number of treatment lines was 4. In the overall population, the objective response rate (ORR) was 72.7%, the disease control rate (DCR) was 90.9%, and the median progression-free survival (mPFS) was six months. Among them, two patients temporarily discontinued treatment after two cycles of T-DXd due to financial reasons, but their disease remained stable for 5 and 8 months, respectively. Efficacy was better in patients with HER-2 amplification, who had not previously used antibody drug conjugates (ADC) drugs, were sensitive to anti-HER-2 treatment, and had ≤3 lines of therapy. Common adverse reactions during T-DXd treatment included gastrointestinal reactions such as nausea, vomiting, diarrhoea, and constipation, as well as haematological toxicities, decreased appetite, hair loss, and fatigue. Some patients experienced gastritis, abnormal liver function, and weight gain, but none of the patients developed interstitial pneumonia. T-DXd can achieve significant and durable survival benefits with controllable safety in patients with HER2-positive or HER2 low-expressing mBC. Key Words: Metastatic breast cancer, Trastuzumab-Deruxtecan, Efficacy, Safety.

Strategic carbon emission assessment in sludge treatment: A dynamic tool for low-carbon transformation

The carbon–neutral target presents a significant challenge for the sewage sludge treatment and disposal (SSTD) industry, necessitating strategic planning for a low-carbon transition. However, flexible and comprehensive carbon emission analysis tools to support this goal remain lacking. This study presents a carbon emission analysis tool to evaluate the carbon emission characteristics and future mitigation potentials of SSTD. The tool integrates life cycle inventory (LCI) modeling-based analysis, sensitivity analysis, regression analysis, and scenario analysis. Carbon emissions are dynamically calculated based on sludge properties, technological level, and industry external parameters, providing a foundation for adaptable evaluation tailored to local conditions. The framework considers the potential effects of multi-parameter and multi-aspect changes in scene design, both within and outside the industry, to achieve dynamic and comprehensive simulations. A case study conducted in Wuhan, China, demonstrated the usability and application processes of the framework. The results indicated that carbon emissions from SSTD are projected to more than double from 2021 to 2060 without interventions. Among the mitigation measures, energy and chemical savings would yield the largest reduction potential, followed by the technical layout adjustment and the promotion of energy efficiency. Operational optimization in the sludge industry and outside the industry would contribute the least. With all mitigation measures applied, emissions could decrease to –82.91 kt CO2-eq in 2060, equivalent to 13.03% compensation for emissions from the sewage treatment line. Among all the processes, incineration routes are recommended due to their current and future low carbon emissions. The cooperative resource route of anaerobic digestion and land use also shows promise as it progressively demonstrates superior performance with increasing organic matter and nutrient content of sludge. Critical factors, sub-processes, and emission types for different routes were identified and can be optimized accordingly. The developed method demonstrates sufficient flexibility to be applied to other cities and larger-scale regions, thereby offering technical and strategic support for SSTD towards carbon–neutral operation.

Trabectedin for L-Type Sarcoma: A Retrospective Multicenter Study

(1) Background: Metastatic L-type sarcomas (liposarcoma and leiomyosarcoma) are rare and have a poor prognosis. Trabectedin is an effective agent that can be used after anthracyclines. This study was designed to evaluate the real-life effectiveness and safety of trabectedin. (2) Methods: A retrospective multicenter study was conducted on patients who were treated with trabectedin for metastatic L-type sarcomas at ten tertiary oncology centers between 2015 and 2023. The objective response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS) were evaluated in the cohort. Cox regression analysis was used to determine prognostic factors for survival. (3) Results: A total of 98 patients (52% liposarcoma and 48% leiomyosarcoma) were included in the study. The median treatment line was three (range: 1 to 6). Thirteen patients (13.3%) underwent local treatment due to oligoprogression, and dose reduction was required in seventeen patients (17.3%) due to toxicity. The ORR and DCR were 16% and 42%, respectively. The median TTF was 3 months, and the median OS was 10 months. In univariate analysis, a significantly longer median TTF was observed in patients who underwent local treatment (p = 0.008), obtained objective responses (p &lt; 0.001), and underwent dose reduction (p = 0.002). No statistical differences were observed according to the histologic subtype and metastatic site. In the multivariate analysis for OS, it was found that obtaining an objective response was a good prognostic factor (p = 0.003), while the presence of liver metastases was associated with a poor prognosis (p = 0.016). (4) Conclusion: Trabectedin is a suitable option for L-type sarcoma after doxorubicin-based treatments. Survival was not worse in patients who underwent dose reduction. The use of local therapies simultaneously with trabectedin can be effective.

End-of-life management of multiple myeloma patients in the era of CD38 and immunotherapy.

In spite of spectacular advances in the treatment of multiple myeloma, a majority of patients will die from this disease or related complications. While a great amount of focus has been dedicated to the development of novel therapies, little attention has been paid to latter stages of patient follow-up. In order to describe patient management during this critical period as well as the immediate causes and circumstances of death, we have analyzed a single center series of 100 patients diagnosed with myeloma who died between 2016 and 2021. Patients received a median of 3 lines of treatment, including 2 during their last year of life. Sixty per cent of patients had received daratumumab. Fifty patients had obtained complete remission or very good partial response at some time during the course of disease but 75 were refractory to the last treatment line. Eighteen patients died while their disease was stable or in remission while 77 had confirmed progressive disease at time of death. Thirty six patients had uncontrolled sepsis, 49 were in renal failure and 24 had hypercalcemia at the time of death. Seventy three patients presented with lymphopenia. Disease progression was documented in a majority of MM patients at the time of death and was associated with disease-related complications in a significant number of patients. Disease progression remains the main cause of death in patients with multiple myeloma.