Future oncology最新文献

Aim: Immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies (MAbs) alone or in combination form the backbone of multiple myeloma (MM) treatment, yet MM remains incurable requiring further lines of therapy (LOT). This study investigated real-world treatment patterns, clinical outcomes, and healthcare utilization among triple-class exposed (TCE) patients initiating subsequent LOTs.

Methods: TCE patients receiving additional LOTs (January 2012-December 2022) in the Alberta Health System databases were included.

Results: Median age among 221 TCE patients requiring subsequent LOT was 70 years. MAbs (42%) and IMiDs (51%) were the most common drug classes incorporated as first and second LOT, respectively. After first LOT, attrition rate was 32%. From first LOT, median time to next treatment or death (TTNT-D) was 10.1 (95% confidence interval: 8.4-13.3) months, median TTNT was 18.1 (15.6-22.4) months and overall survival was 18.7 (16.0-24.3) months. Within first year of subsequent LOT, patients had a median of 1 emergency department visit, 1 hospitalization, 33 clinic visits, 4 infusion appointments, 37 unique healthcare encounters, and a mean of 32 days spent on laboratory tests.

Conclusion: Treatment for TCE patients has limited effectiveness and a high healthcare system burden, emphasizing the unmet need for therapies with novel mechanisms of action.

Breast cancer is a complex disease due to its heterogeneity. While there have been impressive advancements in the treatment of the different breast cancer subtypes, challenges persist when the tumor develops acquired treatment resistance and finally progresses on a given therapy. Since human epidermal growth factor receptor 3 (HER3) plays a key role in developing resistance to several anticancer therapies, many efforts have been performed over the last decades to effectively target HER3. However, most of these attempts have been unsuccessful due to their limited efficacy or severe toxicity. Numerous antibody-drug conjugates (ADCs) targeting HER3 are now being explored. Patritumab deruxtecan (U3-1402; HER3-DXd), the most advanced ADC targeting HER3 in clinical development, has demonstrated significant antitumor activity and a manageable safety profile in patients with breast cancer. This efficacy has been observed across diverse tumor subtypes and varying levels of HER3 expression. In this review, we will analyze the results of clinical trials investigating HER3-DXd in breast cancer and explore its potential role in future clinical applications and treatment algorithms.

Aims: The ALIDHE study aims to supplement previous clinical trial data by evaluating the safety and tolerability of ivosidenib + azacitidine in adult patients with newly diagnosed mutant isocitrate dehydrogenase acute myeloid leukemia (AML).

Methods: Notably, this study has been designed in collaboration with patient representatives from the Acute Leukemia Advocates Network (ALAN) at all stages. Patient representatives from ALAN completed a survey and attended workshops to share feedback on the study design to reduce the burden of participation for patients. Using feedback from ALAN, the study protocol was adjusted to minimize clinical visits and optimize study duration. Quality of life and mental health were included as endpoints in ALIDHE as these outcomes have been recognized as important to capture the lived experiences of patients with AML. Efforts were made to ensure patient comprehension through accessible study documents such as a plain language video and one-page summary.

Conclusions: ALIDHE represents, to our knowledge, the first AML clinical trial that involves patient representatives from development of the study concept to follow-up. ALAN will continue to be involved in ALIDHE as part of the patient steering committee, to ensure that patient perspectives and needs continue to be considered throughout the study duration.

Low-grade serous ovarian carcinoma (LGSOC) is a rare and clinically distinct subtype of ovarian cancer, which presents unique challenges in diagnosis and treatment. LGSOC is characterized by low proliferation rates, high expression of hormone receptors, and frequent alterations in the mitogen-activated protein kinase (MAPK) pathway. Initial standard treatment includes cytoreductive surgery followed by platinum-based chemotherapy and endocrine therapy. However, high recurrence rates (~80%) and poor responses to chemotherapy underscore the urgent need for new treatment strategies. Endocrine therapy is being investigated in the upfront setting, and recent advances in targeted therapies, including MAPK pathway inhibitors and investigational agents such as cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, are shaping the evolving LGSOC treatment landscape. Notably, the recent US Food and Drug Administration approval of the avutometinib/defactinib combination for KRAS-mutated recurrent LGSOC marks a significant milestone in targeted therapy for this disease. Despite these advances, challenges remain in optimizing sequencing strategies and overcoming acquired resistance. This review addresses the importance of understanding the distinct pathophysiology of LGSOC, diagnostic challenges, limitations of conventional treatments, and evolving therapeutic approaches in LGSOC.

Clinical trial registration: ClinicalTrials.gov identifier is NCT06194448 (date of registration 5 January 2024).

Aim: To evaluate the impact of a comprehensive set of social determinants of health (SDOH) on treatments, timing, and key biomarker testing for early-stage non-small cell lung cancer (NSCLC).

Methods: Patients with the first diagnosis of stage I-III NSCLC from 1 January 2015 to 15 October 2023 and treated at community health systems in the United States were eligible for this retrospective database study. We summarized initial primary treatment and time-to-treatment initiation (TTI) by Social Vulnerability Index (SVI), primary care provider (PCP) shortage areas, household income, and insurance type. Data cutoff was 15 October 2024.

Results: Of 8501 patients with stage I-III NSCLC, 32% underwent surgery-only and 14% also received neoadjuvant and/or adjuvant therapy. Greater percentages underwent surgery (with/without neoadjuvant/adjuvant therapy) in counties with lowest SVI/vulnerability, highest median income, and no PCP shortage, and among those with private healthcare insurance (vs. Medicare/Medicaid). Median (range) TTI for any NSCLC-related treatment after diagnosis was 41 days (0-1846); TTI increased across treatment strategies by increasing SVI/vulnerability and decreasing household income. Annual rates of programmed death-ligand 1/EGFR mutation testing rose from 60%/51% in 2020 to 84%/82% in 2023, with greatest rates in counties with no PCP shortage.

Conclusions: Disparities in early-stage NSCLC treatment by SDOH factors call for efforts to improve access to timely care for NSCLC.

Introduction: Breast cancer, due to its heterogeneous nature and variable response to current systemic treatment, can be a great concern. Deregulation of the DNA Damage Response (DDR) pathway genes due to mutation and expression increases cancer risk, progression, and metastasis. The current study was designed to check the expression deregulation patterns of the selected DDR pathway genes (ATM, CHEK1, and CHEK2) at the protein level.

Material & method: Immunohistochemistry-based expression profiling was conducted in 102 histopathological confirmed breast cancer-diagnosed tissues and their adjacent uninvolved control tissues.

Results: Downregulated expression of the selected DDR pathway (ATM, CHEK1, and CHEK2) proteins was observed in breast tumor tissues compared to control tissues. Downregulated protein expression of the DDR pathway genes (ATM, CHEK1, and CHEK2) correlates with aggressive breast cancer phenotypes and increased tumor burden. The selected proteins showed significant diagnostic potential having strong area under curve values for CHEK2 (0.828, p < 0.0001), CHEK1 (775, p < 0.0001) and ATM (0.725, < 0.0001) proteins.

Conclusions: Kaplan-Meier analysis showed that dysregulated expression of these three proteins leads toward poor survival outcomes, suggesting their role to be used as a better and more effective diagnostic and prognostic marker for early diagnosis and effective treatment of breast cancer patients.

Background/objectives: Thyroid-cancer demands age-linked histology and nodule-architecture - factors rarely studied in papillary-thyroid-carcinoma (PTC). Severe-paucity exists in high-quality data about region-specific surveillance and epidemiology.

Methods: We retrospectively analyzed 208-patient-data for prevalences and associations King Salman Specialist Hospital (2022-2025) for age, sex, first-degree-family-history, smoking, obesity (BMI ≥30 kg m^-2), oral-contraceptive-pill (OCP)-use, hypertension, diabetes, nodule-pattern, and tumor-subtype. Associations tested χ² or Fisher's-exact (α = 0.05); effect size as odds ratios (ORs, 95% CI).

Results: Females dominated (70.2%) aged 30-39-years (52.4%). Histology indicated PTC (87.5%), then follicular (8.2%), medullary (3.4%), and anaplastic (1.0%). Age strongly-associated subtype (χ² = 30.7, p < 0.001): PTC comprised 98.2% tumors <40-years but only 72.5% were ≥50-years, where follicular and medullary-cancers reached 27.5%. A positive family-history indicated medullary-carcinoma (11.4% vs 1.7%; χ² = 8.95, p = 0.030; OR = 7.4). Smoking exclusively in men (9.7% vs 0%; χ² = 14.5, p < 0.001). Intriguingly, the novel-finding multinodularity dominating males (43.5% vs 8.9%; χ² = 33.6, p < 0.001) and women-non-users OCPs (32.7% vs 7.3%; χ² = 21.5, p < 0.001) while OCP-use associated to single-nodules warrants investigation. Obesity, hypertension, and diabetes correlated with occurrence.

Conclusions: Thyroid cancer displays age-, sex- and heredity-associations: non-PTC subtypes rose with age, medullary tumors cluster in families, multinodularity predominanted male, and OCP use associated to single-nodules. These findings support age-stratified diagnostics, targeted RET-proto-oncogene-testing, and consideration of hormonal influences.

Aims: This study aimed to describe first-line venetoclax in the Medicare population and its impacts on treatment patterns, utilization, and costs.

Materials and methods: This retrospective cohort study used Medicare Fee-For-Service data from 1 September 2016, to 31 December 2022. Patients were continuously-enrolled, had incident acute myeloid leukemia (AML) and no confounding diagnoses, and were treated with first-line venetoclax-based regimens. Initiation of second line of therapy was modeled using cumulative incidence functions.

Results: Among 2,765 included patients, median age was 76 years. Median venetoclax dosage was 140.4 mg/day - lower than the 400-600 mg/day recommended by clinical guidelines. Patients were less likely to initiate second-line therapy if they were older or had more comorbidities.Patients had a per-month median of 5.3 outpatient visits, 0.3 emergency department visits, and 0.2 hospitalizations; length of stay was 10 days. Mean monthly healthcare costs were $18,092 (SD=$14,289) per patient, with $12,042 (SD=$12,147) and $6,050 (SD=$7,841) attributable to medical services and drug costs, respectively.

Conclusions: A growing number of patients enrolled in Medicare Fee-For-Service with AML use first-line venetoclax. Older patients and those with comorbidities are less likely to initiate second-line therapy. Costs were lower and length of stay was shorter than described in previous research.

Management of penile squamous cell carcinoma (PSCC) remains challenging, with limited effective treatment options. Preclinical studies have shown that combining a PD-1 inhibitor with a PARP inhibitor may produce synergistic antitumor activity. This phase II trial will evaluate the combination of niraparib (PARP inhibitor) with dostarlimab (PD-1 inhibitor) in patients with recurrent or refractory stage III or IV PSCC. The primary endpoint will be the objective response rate (ORR) assessed using iRECIST. Progression-free survival (PFS), overall survival (OS), and safety will be included as secondary endpoints. A first stage cohort of 15 patients will be enrolled; if the ORR exceeds 13%, enrollment will be expanded to include an additional 10 patients in the second stage. If successful, this combination could represent a novel therapeutic strategy for advanced platinum refractory PSCC.Clinical trial registration: www.clinicaltrials.gov identifier is NCT05526989.