Future oncology最新文献

Aims: Lack of diversity in clinical trial populations often results in healthcare inequity. This retrospective analysis presents the impact of implementing inclusive research practices on the diversity of the MyTACTIC trial population.

Patients & methods: Adult patients with advanced solid tumors were enrolled from large academic centers or community cancer clinics and a number of inclusive research practices were implemented to diversify patient recruitment. We summarized race/ethnicity data of the study population related to the sites' catchment area.

Results: Overall, 252 patients were enrolled (83% White). Community clinics represented 95% of screening sites (enrolled 249/252 patients). The proportion of patients from racial/ethnic minorities was generally higher in study centers from ethnically diverse catchment areas. Streamlining the protocol and implementing a free transport scheme to improve patient recruitment yielded positive feedback from site staff; 14 patients (5.5%) used the transportation service.

Conclusion: Findings from the MyTACTIC trial suggest that running trials at community oncology sites does not, by itself, increase patient diversity; other efforts are also necessary. NCT04632992.

Aim: To evaluate the real-world incidence of cardiovascular adverse events (CVAE) and clinical outcomes among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) treated with covalent Bruton's Tyrosine Kinase inhibitors (cBTKis).

Methods: Patients initiating cBTKi treatment from 1 January 2020 to 1 January 2023 were identified using claims data. Demographics, first-line (1L) and second-line or later (2L+) therapy, incident CVAEs, and clinical outcomes were assessed.

Results: In total, 2,163 patients (81.4% in 1L and 18.6% in 2L+) were identified with a mean age of 73.8 $\pm$ 9.2 years and 40.6% female. The most common incident CVAEs were hypertension (23.4%), atrial fibrillation (10.2%), ventricular arrhythmias (10.1%), heart failure (8.5%), and atrial flutter (4.2%). Those with CVAEs experienced higher switching to next treatment + death and worse overall survival than those without CVAEs. Incidence rates were ~2-3 fold lower with acalabrutinib than ibrutinib for hypertension, atrial fibrillation, and atrial flutter. Kaplan-Meier estimates for the likelihood of not experiencing a CVAE were 83% (acalabrutinib) and 72% (ibrutinib) at 12-months.

Conclusions: Despite improvements in 2nd-generation cBTKi cardiotoxicity, patients with CLL/SLL receiving cBTKis have a considerable cardiovascular disease burden. These findings highlight the unmet need for CLL/SLL treatment options with improved efficacy and safety profiles.

Aims: Cancer patients face a higher risk of adverse effects from coronavirus disease 2019 (COVID-19) compared to the general population. However, the safety of restarting antitumor therapy following COVID-19 recovery remains unclear.

Methods: In this prospective, multicenter study conducted between January 1 and 30 March 2023, 419 eligible cancer patients who had recovered from COVID-19 were screened across four medical centers. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs) during the first cycle of antitumor therapy resumed within 3 months after COVID-19 recovery. Changes in clinical laboratory parameters were assessed as secondary endpoints.

Results: A total of 270 eligible participants were included in this study. The common grade 3 or worse TEAEs were fatigue (3.3%), anemia (1.1%), leukopenia (0.7%), and elevated alanine transaminase (0.3%). No severe cardiac toxicity and significant abnormalities on the chest computed tomography (CT) were observed. D-dimer and cardiac troponin I (cTNI) were significantly increased after treatment (p < 0.05). Increased inflammatory cytokines of peripheral blood could be observed after administration of oxaliplatin and trastuzumab.

Conclusions: Restarting systemic antitumor therapy in solid tumor patients after COVID-19 recovery is generally safe. Systemic inflammatory and coagulation function of patients should be monitored during treatment.

Lung cancer is the first cause of mortality and the third most common cancer worldwide. In the United Arab Emirates (UAE), lung cancer ranks third in terms of cancer-related mortality and sixth in terms of incidence. In order to strengthen and to improve the management of this cancer in the UAE, a panel of 15 oncologist and pathologist experts in the field of lung cancer developed the first UAE consensus recommendations for the diagnosis and management of early and advanced lung cancer. A total of thirty-three, statements were drafted, discussed, and voted on, using a modified Delphi process. This consensus meeting acts as a cornerstone for the management of cancers in the UAE and highlights the importance of optimized, evidence-based, and patient-centered practices.

Background/aims: Muscle-invasive bladder cancer (MIBC) has a 5-year survival rate of 40-60% following traditional treatment with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), which significantly impacts quality of life. Bladder preservation strategies, including maximal transurethral resection of the bladder tumor (TURBT), NAC, and radiation therapy, offer similar survival rates with better quality of life. Immune checkpoint inhibitors like avelumab show potential benefits when combined with bladder preservation modalities. This phase II randomized, non-comparative, double-arm, open-label, multicenter trial evaluates the efficacy and safety of two tetra-modality bladder preservation strategies in MIBC patients (T2-T4N0M0). The primary endpoint is the 2-year proportion of bladder-preserved participants. Secondary endpoints include response rates post-induction, quality of life, and safety evaluations.

Methods: Eighty participants will be randomized 1:1 into Arm A or Arm B. All participants will first receive induction chemotherapy (DDMVAC or GC) combined with avelumab, followed by disease evaluation using imaging and TURBT. Those achieving a complete or near-complete response will proceed to hypofractionated radiation therapy (55 Grays in 20 fractions). After radiation, Arm A will receive maintenance avelumab for 1 year, while Arm B will follow a watch-and-wait approach. Non-responders in both arms will be referred for salvage RC.

Clinical trial registration: NCT06686381 (ClinicalTrials.gov).

Aims: Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) inhibitors (PD-[L]1) are standard of care for patients with metastatic non-small cell lung cancer (mNSCLC). This study examined real-world treatment patterns and attrition by lines of therapy (LOTs) among patients with non-driver mutation mNSCLC.

Patients & methods: A retrospective study of adult patients with mNSCLC (2015‒2022) who received ≥1 systemic treatment in COTA's United States multicenter NSCLC database was conducted. Treatment patterns, duration, and outcomes were summarized descriptively. PD-(L)1 utilization was stratified by PD-L1 expression levels (<1%, 1%‒49%, ≥50%).

Results: Among the 2,107 eligible patients, PD-(L)1-based therapy was the most common frontline therapy (55.8%); of these, 60.5% received PD-(L)1/platinum combination therapy. Among PD-(L)1 users, frontline PD-(L)1 monotherapy was most frequently utilized in patients with PD-L1 expression ≥50% (66.2%). Utilization of frontline platinum chemotherapy without PD-(L)1 decreased from 76.8% (2015) to <15% (2019-2022). Mortality across LOTs 1-4 was 37.4%-42.2% and attrition was approximately 60% for each LOT. The overall median duration of LOT1 was 5.4 months. A decreasing trend in the treatment and LOT duration of subsequent LOTs was observed.

Conclusions: Despite incorporating PD-(L)1-based therapies for frontline mNSCLC, mortality and attrition during LOT1 remained high and therapy duration was short, reflecting challenges in managing mNSCLC.

Integrin beta-6 (IB6) is a tumor-associated membrane protein involved in many cellular processes, including wound healing and tissue remodeling. While IB6 expression is constitutively low in healthy tissues, high IB6 expression in numerous cancers, including non-small cell lung cancer (NSCLC), is associated with poor outcomes. In a phase I study, the novel IB6-directed vedotin-based antibody-drug conjugate sigvotatug vedotin (SV) showed manageable safety and encouraging efficacy as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors, including NSCLC. Based on those results, the phase III Sigvie-003 study is evaluating SV plus pembrolizumab compared with pembrolizumab monotherapy as first-line treatment in adult patients with locally advanced, unresectable, or metastatic NSCLC with high programmed cell death ligand 1 expression (tumor proportion score ≥50%). Here, we describe the design of the Sigvie-003 study, which is an open-label, randomized, controlled phase III study. Approximately 714 patients will be randomized 1:1. The dual primary endpoints are progression-free survival as assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors v1.1 and overall survival; secondary endpoints include additional efficacy, safety and tolerability, pharmacokinetics, and immunogenicity endpoints.Clinical trial registration: NCT06758401 (https://clinicaltrials.gov/study/NCT06758401).

Background: There is limited real-world evidence regarding patients with intermediate/poor-risk advanced renal cell carcinoma (aRCC) receiving nivolumab plus ipilimumab (NIVO+IPI) in England. This study aimed to describe characteristics, treatment patterns, and efficacy outcomes in these patients.

Methods: A retrospective chart review of medical records in patients with aRCC receiving NIVO+IPI at any line of therapy between 5 April 2019 and 1 April 2022 in five sites across England was conducted. Data were analyzed descriptively overall, in patients with and without NIVO maintenance after NIVO+IPI initiation, and by prior nephrectomy status.

Results: In total, 128 patients (mean age 60.7 years [standard deviation 10.1], 71.1% male) were eligible; most received first-line (1L) NIVO+IPI (n = 122, 95.3%). Median follow-up was 13.6 months (interquartile range [IQR] 7.1-25.0). Median progression-free survival and overall survival (OS) were 7.6 months (95% confidence interval [CI]: 5.6, 13.1) and 30.7 months (95% CI: 22.5, not reached), respectively. Median OS was not reached in patients who received NIVO+IPI plus NIVO maintenance and patients with prior nephrectomy.

Conclusion: Patients who received NIVO+IPI with NIVO maintenance and patients who had undergone prior nephrectomy experienced the most favorable survival outcomes, aligning with results from previous studies.