Oncologist最新文献

Background: Anitens are a family of oral N-terminal domain (NTD) inhibitors of the androgen receptor (AR). In prostate cancer, they may help overcome AR resistance mechanisms at the ligand-binding domain (LBD), which is the binding site of approved androgen receptor pathway inhibitors like enzalutamide. Masofaniten (EPI-7386) is a next-generation aniten with promising activity and safety in patients with metastatic castrate-resistant prostate cancer (mCRPC).

Methods: In this investigator-initiated, phase II, single arm, single-institution trial, patients with treatment-naïve metastatic hormone-sensitive prostate cancer (mHSPC) were enrolled in a Simon 2-stage study design to receive the combination of masofaniten 600 mg BID and enzalutamide 160 mg daily with androgen deprivation therapy (ADT). The study was designed to enroll 35 patients (13 patients in stage 1, then 22 patients in stage 2). The trial would move to stage 2 if 9 or more subjects achieved a biochemical response at 6 months.

Results: Thirteen patients were screened and enrolled into stage 1. Five were African American, and eight were Caucasian. The median age was 68 years (range 52-75) at time of enrollment. Median follow-up time was 9.9 months (range 7.7-13.6). Ten of 13 patients (77% with 95% confidence interval [CI]: 50% - 92%) achieved a PSA <0.2 ng/mL at 6 months, achieving the threshold to move on to stage 2. Only one patient had disease progression to mCRPC and died of disease at the time of data cutoff. Patients continued enzalutamide and ADT after trial closure.

Conclusion: The combination of masofaniten and enzalutamide for treatment-naïve mHSPC did show efficacy and had an acceptable safety profile. These results support further investigation of the dual AR blockade in mHSPC (ClinicalTrials.gov Identifier: NCT06312670).

Background: Breast cancer survival rates in sub-Saharan Africa are low. In a prospective, multi-center cohort study, we estimated 5-year overall survival rates, overall survival determinants, and mediating effects between socioeconomic status on overall survival among South African women diagnosed with invasive BC.

Patients and methods: Patients from 4 public hospitals were enrolled between July 1, 2015 and January 31, 2019. Survival determinants were assessed using Cox proportional hazard models adjusted for age, background mortality, and treatments. Socioeconomic pathway effects on overall survival were determined through generalized structural equation models.

Results: Of 2838 participants, 58% had advanced-stage (III/IV) disease. Five-year crude overall survival was 44.3% (95% CI 42.5-46.2). Significant mortality risks were late stage at diagnosis (hazard ratio [HR] = 2.31 [95% CI 1.99-2.69] [stage III]; 4.79 [95% CI 3.96-5.80] [stage IV]), HIV-positive status (HR = 1.45 [95% CI 1.25-1.67]), unemployment HR = 1.25 [95% CI 1.09-1.44], and low education HR 1.19 [95% CI 1.04-1.37]). Age and treatment-adjusted socioeconomic status effects on overall survival were mediated through HIV status (81.7% of the effect) and stage at diagnosis (81.7%), both P < .001. Poor breast cancer knowledge had an indirect effect on overall survival, accounting for 77.6% of the total effect (P = .001), fully mediated by late-stage presentation. Socioeconomic status had no significant direct path to mortality after accounting for these mediators.

Conclusion: Interventions should prioritize early breast cancer detection. For patients with low socioeconomic status, particularly those with comorbid HIV, we must mitigate multifaceted barriers to healthcare access, including limited awareness and knowledge of breast cancer.

Choice of oncologist by patients with pancreatic cancer is a complex personal decision. We conducted a retrospective analysis of the Pancreatic Cancer Action Network registry to explore whether age, gender, disease status, feelings of trust and comfort, and the opportunity for clinical trial participation influenced patient choice. Of 110 participants who completed the "Information about Choosing an Oncologist Survey," 68 (61.8%) reported visiting another oncologist. Feeling comfortable and trusting their first oncologist decreased the likelihood of seeking a second opinion (OR: 0.08; CI: 0.01-0.42; P = .005). Patients with resectable disease were also less likely to visit another oncologist compared to patients with borderline resectable or locally advanced disease (OR: 0.28; CI: 0.08-0.95; P = .042). Age, gender, and the opportunity for clinical trial participation did not influence patient choice. Most patients who saw additional oncologists did so because of recommendations from friends or family members. This analysis leveraged patient-reported outcomes to highlight determinants of patient decision-making.

Background: Metastatic urothelial carcinoma (mUC) remains highly lethal despite advances in treatment. There is limited data surrounding the efficacy and toxicity of immune checkpoint inhibitors in treating elderly patients due to the high bar of clinical trial participation. The Geriatric 8 (G8) screening tool is a quick, 8-item questionnaire designed to assess frailty in older adults. This study evaluates the G8 tool's utility in predicting overall survival (OS) and progression-free survival (PFS) in patients with mUC treated with immune checkpoint inhibitors.

Materials and methods: A retrospective analysis was conducted on 48 mUC patients treated with ICI monotherapy at Winship Cancer Institute between 2016 and 2019. Baseline G8 scores were calculated from clinical notes. Primary outcomes included OS and PFS, analyzed using Kaplan-Meier, Cox proportional hazards models, and multivariate analysis adjusted for demographic and clinical variables.

Results: An impaired baseline G8 score predicted worse OS but not PFS. The incidence of immune-related adverse events was lower but not statistically significant in patients with impaired G8 scores (HR, 0.31; OR, 0.09-1.14; P = .077).

Conclusion: The G8 screening tool effectively predicts OS in older mUC patients treated with ICIs, highlighting its potential utility in clinical decision-making. Frail patients, as identified by the G8, had significantly worse survival outcomes, underscoring the need for tailored therapeutic approaches in this vulnerable population. Further studies are warranted to validate these findings and explore interventions that may improve outcomes for frail, older patients with mUC.

Background: Febrile neutropenia (FN) is a common complication with myelosuppressive chemotherapy regimens, significantly affecting patients with breast cancer (BC) receiving docetaxel and cyclophosphamide (TC). Treatment with granulocyte colony-stimulating factor (G-CSF) is established for prophylactic and therapeutic use to reduce risk of FN. Eflapegrastim-xnst, a novel long-acting G-CSF, has a favorable safety profile and is effective in reducing neutropenia risk in patients with early-stage BC receiving TC, when administered 24 h after chemotherapy. The benefits of eflapegrastim-xnst given same day as TC have not been evaluated in a randomized controlled trial.

Patients and methods: This phase 1, multicenter, open-label trial evaluated efficacy and safety of eflapegrastim-xnst administered 0.5 h post-TC chemotherapy for four cycles in patients with early-stage BC. The primary end point was time to recovery of absolute neutrophil count (ANC) from nadir to ≥1.5 × 109/L in cycle 1. Secondary end points included safety, duration of severe neutropenia, incidence of FN, and neutropenic complications.

Results: Of 53 patients enrolled, 49 completed the study. Mean time to ANC recovery in cycle 1, the primary end point, was 1.8 days. Only 1 patient (2%) experienced an FN episode in cycle 1 (1 episode/228 cycles received [0.4%]). Incidence of severe neutropenia decreased from 42.9% (cycle 1) to 27.3% (cycle 4). Eflapegrastim-xnst was well tolerated; common treatment-emergent adverse events included fatigue, nausea, alopecia, and bone pain.

Conclusions: Eflapegrastim-xnst, administered same day as TC chemotherapy was effective and well tolerated evidenced by short time to neutrophil recovery and low incidence of FN, with an adverse event profile similar to that of next-day dosing.

Melanoma of unknown primary (MUP) is a rare subtype of melanoma, with its low incidence posing challenges for clinical management. This systematic review integrates recent advances in MUP research, with a focus on pathogenesis, molecular characteristics, and therapeutic strategies. The proposed pathogenesis involves spontaneous regression of the primary lesion, potentially driven by sequential immune responses mediated by T cells and natural killer cells. At the molecular level, whole-exome/genome analyses reveal that MUP and cutaneous melanoma share a highly concordant UV damage-driven mutational landscape; nevertheless, MUP exhibits distinct genomic alterations, including recurrent mutations in the telomerase reverse transcriptase promoter, protein phosphatase 6 catalytic subunit, and isocitrate dehydrogenase 1. Current therapeutic approaches are similar to those for advanced melanoma, encompassing surgery, immune checkpoint inhibitors (ICIs), and targeted therapies. While ICIs have demonstrated significant improvements in survival, the clinical efficacy of targeted therapies in MUP remains to be fully established. By consolidating current knowledge, this review provides insights to guide diagnosis, treatment, and future research in MUP.

Background: People living with HIV (PWH) have an increased risk of developing aggressive skin cancers, yet they have been largely excluded from immune checkpoint inhibitor (ICI) trials. Consequently, evidence on the safety and efficacy of ICIs in this population remains scarce, particularly for the nivolumab plus ipilimumab (NIVO+IPI) combination.

Methods: This multicentre, real-world study included PWH treated with ICIs for melanoma or non-melanoma skin cancers. The objective was to evaluate patient characteristics, treatment management, and clinical outcomes across the different skin cancer types.

Results: Among the 54 patients, 89% were male, and 92.6% had a suppressed HIV viral load. Melanoma was the most frequent tumour (35/54, 64.8%), followed by cutaneous squamous cell carcinoma (12/54, 22.2%), Kaposi sarcoma (4/54, 7.4%), basal cell carcinoma (2/54, 3.7%), and one Merkel cell carcinoma. Anti-PD-1/PD-L1 monotherapy was given as first-line treatment in 81.5% (44/54). Immune-related adverse events (irAEs) occurred in 42.6% (23/54), with a median onset of 43.5 days (IQR, 20.5-126). The maximum toxicity grade was 1/2 in 39% (21/54), grade ≥ 3 in 13% (7/54). Seventeen melanoma patients received NIVO+IPI. Among them, 64.7% (11/17) experienced irAEs, including grade ≥ 3 events in 30% (5/17). Objective response rates were 43% (9/21) in melanoma, 58% (7/12) in cSCC, and 75% (3/4) in Kaposi sarcoma.

Conclusions: PWH treated with ICIs for skin cancer demonstrated favourable outcomes, with a notably reassuring safety profile of NIVO+IPI. These findings support managing well-controlled PWH similarly to the general population and highlight the importance of including this population across all settings of skin cancer trials.

Background: It has been hypothesized that sequencing antigen-directed immunotherapy with immune checkpoint inhibitors could prime a tumor for immune response to immune checkpoint inhibitors.

Methods: This study (NCT03072160) was designed to evaluate two cohorts of patients with medullary thyroid cancer, a cancer that is not known to have therapeutic responses to immune checkpoint inhibitors. One cohort included patients with previous immunotherapy (GI-6207, an experimental therapeutic cancer targeting carcinoembryonic antigen), and a second cohort included patients with no previous history of GI-6207. All patients were treated with standard of care dosing of pembrolizumab, 200 mg every 3 weeks for up to 2 years. Patients were followed with imaging every 3 months. Peripheral blood mononuclear cells (PBMCs) were evaluated at 3 months for immune responses.

Results: 17 patients were enrolled on this study. Among the 13 patients with previous immunotherapy (GI-6207), the median age was 52.4 years. Among the 4 patients with no previous immunotherapy the median age was 58.8 years. No patients in either cohort had evidence of therapeutic response. No patients had confirmed 50% declines in either serum carcinoembryonic antigen or calcitonin. No radiographic responses were observed. There was no evidence of immune impact of pembrolizumab in analysis of PBMCs. Given the lack of responses in the previous immunotherapy cohort, the study was closed early. No new safety signals were observed.

Conclusions: This study did not support the hypothesis that sequencing immunotherapy with an immune checkpoint inhibitor could enhance the clinical activity of the immune checkpoint, which has not demonstrated independent activity in that disease previously.

Background: Trastuzumab deruxtecan (T-DXd), an approved human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate, may cause treatment-emergent adverse events (TEAEs), most commonly gastrointestinal and hematologic TEAEs. This pooled analysis evaluated TEAEs across 2 doses of T-DXd in patients with different cancers to support safe and effective real-world use.

Patients and methods: Data were pooled from 9 phase I-III clinical trials (DS8201-A-J101; DESTINY-Breast01/02/03/04; DESTINY-Lung01/02; DESTINY-Gastric01/02) of T-DXd 5.4 or 6.4 mg/kg every 3 weeks in patients (N = 1678) with metastatic breast, gastric, or lung cancer with varying HER2 expression or HER2 mutation status. Nausea, vomiting, neutropenia, fatigue, and interstitial lung disease (ILD) were evaluated for time to onset and dose-related outcomes. Antiemetic analysis was limited before a 2020 protocol change recommending prophylaxis.

Results: Common TEAEs (in ≥20%) were fatigue, nausea, vomiting, neutropenia, anemia, and thrombocytopenia; mostly grade 1 or 2. TEAEs leading to dose reduction, drug interruption, and discontinuation with T-DXd were 22.6%, 42.8%, and 17.7% (5.4 mg/kg), and 29.7%, 47.6%, and 16.6% (6.4 mg/kg), respectively. Neutropenia, nausea, and fatigue occurred in 34.6%, 74.6%, and 56.5% of patients (5.4 mg/kg) and 49.3%, 65.5%, and 52.8% (6.4 mg/kg). Adjudicated drug-related ILD occurred in 12.0% and 10.9%, respectively.

Conclusion: Gastrointestinal and hematologic TEAEs were most common, with nausea, neutropenia, and fatigue most commonly reported. ILD/pneumonitis occurred in ∼11%-12% of patients, with severe cases infrequent. Most TEAEs were low grade, though dose modifications highlight the need for proactive TEAE management, particularly in older patients and those with renal impairment.

Background: The emergence of neoadjuvant immunotherapy has improved outcomes for hepatocellular carcinoma (HCC) patients, yet early postoperative recurrence remains a critical challenge. This study aimed to identify clinicopathological and immune microenvironment features associated with recurrence-free survival (RFS) and develop a predictive model for early recurrence in HCC patients undergoing neoadjuvant anti-PD-1 antibody therapy.

Materials and methods: Clinicopathological characteristics and immune microenvironment profiles were analyzed in 70 HCC patients treated with neoadjuvant anti-PD-1 antibody and 20 patients receiving transarterial chemoembolization (TACE). Key variables, including microvascular invasion (MVI), tumor capsule integrity, and immune cell infiltration, were evaluated. Statistical analyses included multivariate Cox regression, Kaplan-Meier survival analysis, and nomogram construction with internal validation to predict recurrence risk.

Results: Foam cell response and tumor-infiltrating lymphocytes (TILs) were strongly linked to favorable immunotherapy responses. Patients without MVI, those with intact tumor capsules, and those exhibiting high CD4+ T cell density in central tumor regions demonstrated significantly prolonged RFS. A nomogram integrating these three factors achieved robust predictive accuracy for early recurrence stratifying patients into distinct risk groups.

Conclusions: This study highlights MVI absence, tumor capsule integrity, and CD4+ T cell infiltration as key predictors of RFS in HCC patients receiving neoadjuvant immunotherapy. The proposed nomogram provides a clinically actionable tool for early recurrence risk assessment, enabling personalized postoperative monitoring and adjuvant therapy strategies to improve survival outcomes.