Future oncology最新文献

Patients diagnosed with metastatic basal cell carcinoma (BCC) have a poor prognosis. The current standard of care for adults with locally advanced or metastatic BCC who are not candidates for surgery or radiation therapy is treatment with hedgehog pathway inhibitors (HHIs). For patients who progress while on this therapy, further treatment options are limited. There is also a need for real-world clinical practice data on the clinical characteristics, management, disease progression, and survivorship of these patients. The ongoing CemiplimAb-rwlc Survivorship and Epidemiology (CASE) study is a phase IV, multicenter, prospective, noninterventional survivorship and epidemiology cohort study evaluating the effectiveness and safety of cemiplimab, a fully human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death-1 (PD-1) receptor and its ligands. This paper describes one cohort of the CASE study of patients with locally advanced or metastatic BCC who have failed or are intolerant of HHIs or for whom HHI therapy is not appropriate. Outcome measures of the study include response to treatment, quality of life, safety, treatment patterns, patient experience, and survival. This study could provide a more complete characterization of this patient population and fill knowledge gaps related to real-world treatment utilization and patient outcomes.Clinical Trial registration: NCT03836105.

Introduction: The treatment landscape of metastatic urothelial carcinoma (mUC) has evolved with the emergence of programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitors. This study assessed mUC treatment patterns in Europe.

Methods: Data were derived from the Adelphi mUC Disease Specific Programme™ (November 2020 to April 2021), a large, cross-sectional, patient record-based survey of physicians in France, Germany, Italy, Spain, and the United Kingdom. Patient characteristics, treatment patterns across lines of therapy, and treatment durations were assessed.

Results: Physicians (N = 232) provided data for 1922 patients with mUC. Mean (SD) patient age at the time of data collection was 69.1 (7.9) years, and 81% presented with bladder tumors. Most patients received platinum-based chemotherapy in first-line (cisplatin plus gemcitabine, 43%; carboplatin plus gemcitabine, 28%), followed by PD-1/L1 inhibitors in second-line (pembrolizumab, 35%; atezolizumab, 19%). In third-line, 41% received best supportive care and 36% received single-agent chemotherapies. Mean treatment duration was longer in second-line than first-line (6.1 vs 4.8 months).

Conclusions: Most patients received platinum-based chemotherapy in first-line, followed by a PD-1/L1 inhibitor. A substantial proportion received best supportive care after second-line. Findings indicate unmet need for the later-line treatment of mUC and provide important context for the emergence of novel therapies.

Background: The treatment landscape of non-metastatic non-small cell lung cancer (NM-NSCLC) is rapidly evolving with recent approvals of immunotherapies and targeted therapies.

Methods: This retrospective study included 202 adults diagnosed with NM-NSCLC between 1 January 2018 and 31 December 2020 primarily aiming to capture initial management strategies.

Results: Most frequent treatment patterns among Stage I/II patients (N = 84) were surgery only (48.8%) and surgery with adjuvant chemotherapy (with/without RT; 42.9%). Among Stage III patients (N = 118), most frequent patterns were chemotherapy plus radiotherapy (44.9%) and chemotherapy only (18.6%); 58.6% of Stage IIIA patients underwent surgery (of these, 32.4% also received chemotherapy and radiotherapy).

Conclusion: Initial strategy was aligned with contemporary at that time European guidelines, setting a benchmark for understanding the future uptake of new therapies.

Seizures are a frequent complication in glioma. Incidence of brain tumor-related epilepsy (BTRE) in high-grade glioma (HGG) is an estimated > 25% and in low-grade glioma (LGG) is approximately 72%. Two first-line antiseizure medications (ASMs) for BTRE include levetiracetam (LEV) and valproic acid (VPA). Use of VPA has decreased because of a broader side effect profile, potential interaction with chemotherapeutic drugs, and availability of newer generation agents. In refractory BTRE, LEV and VPA may be prescribed together to enhance seizure control. VPA and LEV have gained attention for their purported antineoplastic effects and synergistic role with temozolomide. VPA is suggested to modulate anticancer activity in vitro through multiple mechanisms. In addition, retrospective studies indicate increased overall survival in patients with epileptogenic HGGs who are managed with LEV or VPA rather than other ASMs. However, these studies have numerous limitations. It is also reported that patients with glioma and a seizure history have a longer survival. This extended survival, if one exists, may be only observed in certain gliomas with corresponding patient characteristics. We provide a brief overview of the management of BTRE, VPA and LEV as anticonvulsants and antineoplastics, and the factors that may be associated with survival in epileptogenic glioma.

Esophageal squamous cell carcinoma (ESCC) is a severe malignant tumor of the digestive system that poses a significant threat to human health. Despite its significance, the complex molecular mechanism regulating the occurrence and development of ESCC remain elusive. The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) members constitute a pivotal subfamily of the APOBEC family that possess cytidine deaminase activity. In recent years, APOBEC3s (A3s) have received increasing attention due to their pivotal roles in the occurrence, development, and prognosis of ESCC. This comprehensive review systematically summarizes the latest research progress on the mechanisms of action of A3s in ESCC and discusses their impact on the development and therapeutic considerations for ESCC, with a particular focus on their potential role in immunotherapy. These insights may be of great value in continued exploration of ESCC pathogenesis and provides a theoretical foundation for the development of clinical treatment strategies for ESCC.

Aims: This study aimed at developing a scoring system (EAST score) to predict recurrence after chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC).

Patients & methods: Treatment-naïve LS-SCLC patients receiving concurrent chemoradiotherapy (CCRT) (N = 234) or sequential chemoradiotherapy (N = 53) were retrospectively reviewed. Using data from CCRT population, clinical and radiological variables associated with disease progression were identified. Selected variables were assigned numerical scores based on their estimated hazard ratios (HRs), and the EAST score was established.

Results: EAST score incorporated N3 disease and serum biomarkers (lactate dehydrogenase, pro-gastrin-releasing peptide, and cytokeratin-19 fragment). In the CCRT population, progression-free survival (PFS) was significantly shorter in the high-risk group (EAST score ≥ 2) than the low-risk group (EAST score ≤ 1) (median, 9.4 months vs. 20.6 months; HR [95% confidence interval (CI)], 2.09 [1.50-2.91]). As for the model performance, the 1- and 2-year area under the curve values for PFS were 0.68 and 0.65, respectively. Overall survival was also shorter in the high-risk group (HR [95% CI], 1.49 [1.02-2.16]). Similar trends were observed in the sequential chemoradiotherapy population (HR for PFS [95% CI], 2.43 [1.07-5.53]).

Conclusions: EAST score effectively predicts recurrence risk in LS-SCLC, demonstrating the necessity for developing new treatment strategies for high-risk patients.

Patients diagnosed with metastatic colorectal cancer (mCRC) have a poor prognosis with survival ranging 2-3 years. The prevalence of human epidermal growth factor receptor 2 (HER2) amplification is approximately 3-4% in mCRC and increases up to 8% in patients with KRAS/NRAS/BRAF wild-type (WT) CRC tumors. Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor that, in combination with trastuzumab, has demonstrated clinically meaningful activity in patients with chemotherapy-refractory, HER2-positive (HER2+), RAS WT mCRC in the MOUNTAINEER trial. The MOUNTAINEER-03 phase III trial is designed to investigate the efficacy and safety of first-line tucatinib in combination with trastuzumab and modified FOLFOX6 (mFOLFOX6) versus standard of care (mFOLFOX6 plus bevacizumab or cetuximab) in patients with untreated HER2+, RAS WT locally advanced unresectable or mCRC. MOUNTAINEER-03 will include two arms of approximately 400 patients randomized 1:1 to either treatment arm. The primary endpoint is progression-free survival per RECIST v1.1 by blinded independent central review (BICR). Key secondary endpoints are overall survival and confirmed objective response rate (according to RECIST v1.1 per BICR). Safety assessments will include surveillance and recording of adverse events, physical examination findings, vital signs, cardiac assessments, Eastern Cooperative Oncology Group performance status, concomitant medications, and laboratory tests.Clinical trial registration: NCT05253651 (ClinicalTrials.gov).

Metastatic prostate cancer remains incurable. Though significant progress has been made in the field, the search for agents that improve outcomes for patients is ongoing. Several clinical trials have explored the benefit of combining PARP inhibitors (PARPi) with androgen receptor pathway inhibitors (ARPIs) for metastatic castrate resistant prostate cancer (mCRPC), especially those cancers with alterations in homologous recombination repair (HRR) genes. Niraparib, a highly selective inhibitor of PARP1 and PARP2, has been shown to confer a radiographic progression-free survival benefit in the treatment of mCRPC with HRR-associated gene alterations, particularly BRCA1 and BRCA2 (BRCA1/2), when combined with abiraterone acetate plus prednisolone (AAP). This combination has recently been approved in the USA, Canada and Europe for patients with mCRPC and a BRCA1/2 gene mutation. This review summarizes the evidence with regards to the pharmacologic activity and clinical efficacy of niraparib with a specific focus on its efficacy in combination with AAP in mCRPC patients with HRR alterations.