Future oncology最新文献

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.

Aims: This retrospective, chart-review study evaluated real-world outcomes post-frontline brigatinib in ALTA-1L.

Methods: Patients from ALTA-1L were followed after brigatinib discontinuation. Outcomes evaluated for second-line (2L) treatment included real-world overall response rate (rwORR), time to treatment discontinuation (rwTTD), and progression-free survival (rwPFS).

Results: Forty of 48 patients received subsequent systemic anticancer therapies; 30 received 2L ALK tyrosine kinase inhibitors (TKIs), mostly lorlatinib (n = 16) or alectinib (n = 8), and 11 received 2L non-ALK TKI therapy (one with alectinib). rwORR was 33% with 2L ALK TKIs and 0% with 2L non-ALK TKI therapy. Median (95% confidence interval [CI]) 2L rwTTD was 34.7 months (4.6-not reached [NR]) for ALK TKIs (lorlatinib, 37.2 months [6.0-NR]; alectinib, NR [1.1-NR]; crizotinib, 2.8 months [2.0-NR]) and 4.4 months (1.4-6.0) for 2L non-ALK TKI therapy. Median (95% CI) 2L rwPFS was 16.1 months (4.4-NR) with ALK TKIs (lorlatinib, 25.6 months [3.8-NR]; alectinib, 16.1 months [1.1-NR]; crizotinib, 2.4 months [2.0-NR]) and 6.1 months (1.7-NR) with 2L non-ALK TKI therapy.

Conclusions: Following brigatinib discontinuation, most patients initiated a second ALK TKI. Patients treated with 2L second- or third-generation ALK TKIs post-brigatinib experienced prolonged clinical benefit.

Clinical trial registration: clinicaltrials.gov identifier: NCT02737501.

Vasculogenic mimicry (VM) allows tumor cells to form vessel-like channels, promoting growth, metastasis, and therapy resistance. Persistent infection with high-risk human papillomavirus (HPV), mainly types 16 and 18, is a key factor in various cancers, including anogenital and head and neck cancers. VM has been documented in cervical cancer and oral squamous cell carcinoma (OSCC), but its role in other HPV-associated cancers remains unexplored. This review summarizes literature published between October 2024 and April 2025 in PubMed and Google Scholar, focusing on VM in HPV-related cancers. General mechanisms highlighted include epithelial-mesenchymal transition, hypoxia, and activation of STAT3 and PI3K/AKT pathways. Molecular regulators include TXNDC5, CHI3L1, erythropoietin, and microRNAs miR-124 and miR-29b in cervical cancer; and collagen XVI, LGR5, ALDH1, Beclin 1, VE-cadherin, CD44, HIF-1α, and SOX7 in OSCC. From a translational perspective, elucidating the molecular regulators of VM could reveal therapeutic opportunities through strategies targeting specific signaling pathways in tumor cells.