Oncologist最新文献

Background: The symptom burden associated with advanced pancreatic cancer, such as metastatic pancreatic adenocarcinoma (mPC), reduces patients' health-related quality of life (HRQoL). Recognizing the impact of disease- and treatment-related symptoms is essential in refining patient-reported outcomes (PROs) in clinical research, ensuring that PRO measures in clinical trials support US Food and Drug Administration label statements, and improving patient HRQoL.

Patients and methods: Patients with mPC and caregivers of patients with mPC were interviewed for this qualitative study. Insights from interviews were used to update a preliminary conceptual model derived from a targeted literature review. The primary objective was to obtain an in-depth understanding of patients' experience of living with mPC and the impact of mPC on patients' lives.

Results: Across 19 interviews (n = 16 patients, n = 3 caregivers), the most frequently reported symptoms were tiredness (n = 19); fatigue, nausea, and weight loss (n = 18 each); and diarrhea and hair loss/thinning (n = 16 each); 17 participants reported mPC- and/or treatment-related pain. The most frequently reported impacts were anxiety (n = 17), reduced physical functioning (n = 16), and worry/fear of disease (n = 16). After identification of the most salient symptoms and impacts, two symptoms and four impacts were added to the preliminary conceptual model and 31 symptoms and 11 impacts were removed to generate the final conceptual model (40 symptoms and 26 impacts).

Conclusion: This qualitative interview study uncovered previously unreported symptoms and impacts of mPC and supports the careful selection of appropriate PRO measures that more comprehensively reflect the experience of patients with mPC in future clinical trials.

Background: The age-specific distribution of frailty and its domain-level characteristics remain poorly understood across the adult population of patients with cancer. We aimed to quantify the frailty prevalence and geriatric assessment (GA) impairment patterns in adults and to examine their prognostic relevance in newly diagnosed patients with cancer.

Material and methods: This multicenter, cross-sectional cohort enrolled 2,501 adults (≥20 years) before therapy in 2021-2023. GA covered 8 domains (function, comorbidity, cognition, mood, nutrition, polypharmacy, falls, and social support). Patients were grouped into 6 age bands (20-39 to ≥80) and labeled fit (0 deficits), prefrail (1), or frail (≥2). We analyzed age-specific geriatric impairment patterns and overall survival (OS).

Results: The mean number of GA deficits increased significantly across the 6 ordered age bands. Frailty was common and increased with age: 40.0% (20-39), 42.3% (40-49), 56.2% (70-79), and 74.4% (≥80). Malnutrition was the most frequent deficit (59.1% overall), affecting 51% of patients aged 20-39 years, peaking at 63.8% in the 70-79-year cohort. Older age groups showed steeper increases in comorbidities, cognitive impairment, and functional decline. Polypharmacy and depressed mood were frequent, but varied less with age; inadequate social support was uniformly low. In multivariable models, prefrailty and frailty predicted worse OS. Age-stratified analyses of 40-49, 50-59, and 70-79-year cohorts showed similar associations.

Conclusion: Frailty is prevalent across adults of all ages with distinct, age-associated GA profiles. Nutritional deficits were the most prevalent impairment even among younger adults, whereas functional, comorbidity, and cognitive burdens escalate in older patients with cancer. Routine pretreatment GA for all adults can identify vulnerabilities and enable age-tailored supportive interventions.

Background: Overall survival (OS) is the gold standard endpoint in oncology trials but requires long follow-up and may be confounded by post-protocol treatments. Radiographic progression-free survival (rPFS) is used as an earlier endpoint in metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the validity of rPFS as a surrogate for OS in first-line, asymptomatic/mildly symptomatic, androgen receptor pathway inhibitor (ARPi) naïve, mCRPC using methods recommended by Germany's Institute for Quality and Efficiency in Health Care (IQWiG).

Materials and methods: A systematic search in Ovid® identified randomized controlled trials reporting both rPFS and OS. Trial-level rPFS-OS correlations of hazard ratios (HRs) were calculated using bivariate random-effects meta-analysis (BRMA) and weighted linear regression (WLR). Correlation strength was interpreted per IQWiG criteria. The surrogate threshold effect (STE) was estimated to assess surrogacy. Leave-one-out cross-validation (LOOCV) assessed model robustness. The primary analysis included trials meeting the proportional hazards (PH) assumption. Sensitivity analyses included trials violating PH and further excluded outliers outside the 95% confidence intervals (CIs) in the correlation plot.

Results: Eleven RCTs were identified. The primary analysis (n = 10 trials) yielded medium correlations (BRMA R2: 0.78 [95% CI: 0.53-0.90]; WLR R2: 0.65 [0.40-0.90]; STE: 0.83). Sensitivity analyses yielded medium (n = 11 trials) and strong (n = 8 trials) correlations. LOOCV showed good predictive accuracy (75%-82%).

Conclusion: Results suggest rPFS is a valid surrogate for OS in first-line ARPi naïve mCRPC per IQWiG criteria. A statistically significant OS effect can be inferred for a trial demonstrating an upper confidence limit of HR < 0.83 in rPFS.

Background: Payments from pharmaceutical companies to oncologists can influence prescribing practices. However, some physicians believe that receiving payments from multiple competing manufacturers might balance these biasing effects, effectively "canceling out" any conflict of interest. This study examines how often physicians receive industry payments for multiple, competing drugs.

Methods: Using the CMS Part D Prescribers file 2017-2019, we included medical oncologists who prescribed a class of cancer drugs wherein there are multiple, competing drugs. We then matched these oncologists to their industry payments records (Open Payments). We assessed the proportion of oncologists who received any industry payments related to 0, 1, 2, or 3 of the competing drugs, and whether oncologists prescribed differently with respect to the number of drugs for which they received payment.

Results: Among 2460 eligible oncologists, a minority received payments related to all 3 competing drugs within the drug class they prescribed: 1.6% of oncologists prescribing epidermal growth factor receptor inhibitors, 25.3% for BCR-ABL tyrosine kinase inhibitors, and 34.3% for CDK4/6 inhibitors. Oncologists who received payments for all 3 drugs were more likely to prescribe ribociclib versus palbociclib, and less likely to prescribe dasatinib, compared to unpaid oncologists. Those who received payments for 2 drugs were more likely to prescribe afatinib versus osimertinib.

Conclusions: Receipt of payments from all competing companies occurs among a minority of oncologists, but a substantial minority for some drug classes. Oncologists who receive payments from multiple companies have different prescribing patterns than unpaid oncologists, suggesting that competing payments may not result in "balanced" influence.

Background: This phase II trial prospectively assessed the efficacy and safety of induction chemoimmunotherapy followed by sequential concurrent chemoradiotherapy plus immunotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were ineligible for surgery.

Methods: Forty-four patients received 2 cycles of induction therapy (paclitaxel plus carboplatin/nedaplatin combined with a PD-1 inhibitor), followed by concurrent radiotherapy with two additional cycles of chemoimmunotherapy and subsequent immune maintenance therapy for up to 1 year. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life (QoL).

Results: At the data cut-off point (median follow-up: 25.5 months), both the ORR and DCR were 95.5%. The median PFS was 26 months (95% CI, 14.8-37.2), and the median OS was 29 months (95% CI, 23.0-35.0). The 1-, 2-, and 3-year PFS rates were 75.0%, 51.9%, and 40.4%, respectively, and the OS rates were 81.8%, 63.1%, and 42.0%, respectively. Distant metastasis represented the main failure mode (64.0%). Treatment-related adverse events were generally mild; moreover, 17 patients (38.6%) experienced grade ≥3 events, primarily involving hematologic toxicity (14/17). Severe immune-related adverse events were rarely observed. QoL assessment in surviving patients (n = 21) indicated favorable overall function and well-being.

Conclusions: This regimen of induction chemoimmunotherapy followed by concurrent chemoradiotherapy and maintenance immunotherapy demonstrated promising survival outcomes, a manageable safety profile, and a preserved QoL, thereby offering a viable nonsurgical alternative for patients with locally advanced ESCC.

Background: QUALIOR-phase 2 multicenter trial explored the feasibility of a home-based supervised physical exercise program (SPEP) in metastatic cancer patients receiving oral targeted therapies.

Methods: Patients with metastatic cancers receiving oral targeted therapies were randomized (2:1) to a 3-month home-based SPEP (with a coach at home) or recommended adapted physical exercises (booklet). Primary endpoint was feasibility defined as the rate of patients who performed at least 50% of the theoretically planned sessions in the SPEP arm. Main secondary endpoints were fatigue and pain evaluated by visual analogue scales (VAS) during the program.

Results: Among 112 patients, 74 and 38 were included in the SPEP and control arms, respectively. Median age was 59 (range: 31-83) years and the majority of patients were women. Main primary tumor location was breast (57%) and kidney (16%). Thirty-three (30%) patients were treated with anti-angiogenic tyrosine kinase inhibitors, and 53 (47%) received epidermal growth factor receptor or cell cycle inhibitors. Forty-five (61%) patients performed at least 50% of the SPEP. Median fatigue decreased from 4 to 3 (range: 0-10) after 3 months in the SPEP group with maintain of pain control. The percentage of patients with high level VAS of fatigue at 3 months was lower in SPEP arm than in the control arm (27% vs. 62%, P = .004).

Conclusions: QUALIOR showed that SPEP with a coach at home was feasible in patients with metastatic cancers treated with oral targeted therapies. This program could mitigate the fatigue induced by oral targeted therapies.

Background: APX3330 is an oral agent targeting the redox signaling activity of APE1/Ref-1 (Ref-1), a key regulator of transcription factors involved in inflammation and tumorigenesis. APX3330 selectively inhibits Ref-1's redox function without affecting its DNA repair role. This Phase 1, multicenter, open-label, dose-escalation study in advanced solid tumors was aimed at determining the recommended Phase 2 dose (RP2D) while assessing safety, pharmacokinetics, and biomarker evidence of target engagement.

Methods: Nineteen cancer patients were treated, with eight completing follow-ups. Subjects received APX3330 orally twice daily in 21-day cycles, starting at 240 mg/d and escalating in 120 mg/d increments. Adverse event (AE) monitoring followed a 1 pt/cohort approach until a >G2 toxicity event, after which a 3 + 3 design was implemented. Treatment continued until disease progression, consent withdrawal, or intolerable toxicity. Antitumor activity was assessed using RECIST 1.1, and pharmacodynamic markers included serum Ref-1 levels and circulating tumor cells.

Results: Six of nineteen subjects had stable disease, and no treatment-related SAEs were observed. One subject (720 mg cohort) withdrew due to Grade 3 maculopapular rash (dose-limiting toxicity). Laboratory assessments and ECGs showed no clinically significant abnormalities.

Conclusions: APX3330 showed preliminary signals of disease control and on-target pharmacology in this first-in-human study. Based on safety and PD, the RP2D is 600 mg/d. Given the small sample size, efficacy conclusions are exploratory (ClinicalTrials.gov Identifier: NCT03375086).

Background: Anitens are a family of oral N-terminal domain inhibitors of the androgen receptor (AR). In prostate cancer, they may help overcome AR resistance mechanisms at the ligand-binding domain, 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 8 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% 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).