Future oncology最新文献

Background: Atezolizumab plus bevacizumab (atezo+bev) is a standard-of-care 1L treatment for unresectable hepatocellular carcinoma (uHCC). Understanding its adoption and use, clinical outcomes, and subsequent therapies are needed.

Methods: This retrospective cohort study included 550 patients with uHCC in the US who initiated 1L atezo+bev between June 2020 and April 2023. Medical records were abstracted to describe treatment patterns and outcomes.

Results: Of 294 patients who discontinued 1L therapy, 176 patients initiated 2L therapy (2L cohort) and 48 patients didn't initiate 2L therapy after ≥8 weeks of follow-up (No 2L cohort). More of the No 2L cohort had Stage IVb tumors, BCLC stage D, ECOG-PS ≥2, ascites, and hepatic encephalopathy at baseline. The 2L cohort were more likely to discontinue atezo+bev due to disease progression (92.1% vs. 56.3%), and less likely due to toxicity/intolerability (4.0% vs. 10.4%) than the No 2L cohort. OS from 1L atezo+bev initiation was significantly longer in the 2L cohort vs. No 2L cohort (median 23.0 vs. 14.3 months; p < 0.001]).

Conclusions: 1L Atezo+bev was clinically active with 256 patients remaining on therapy at last follow-up. Patients who progressed after 1L atezo+bev benefited from additional systemic therapies. Future research analyzing the comparative effectiveness of 2L therapies is needed.

Introduction: Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 5% of cancer cases worldwide, with more than half of patients presenting with locally advanced (LA) disease. Treatment of LA HNSCC is multimodal and may include concomitant cisplatin-based chemoradiotherapy (CRT) or surgery; however, recurrence rates are high, and there is an unmet need for new treatments. Immune checkpoint inhibitors that target programmed death receptor-1 (PD-1) are standard of care for recurrent/metastatic HNSCC, but outcomes for anti-PD-1 and anti-PD-(ligand [L])1 therapies with CRT in LA HNSCC have been variable. Dostarlimab, an anti-PD-1 therapy approved in advanced endometrial cancer and mismatch repair-deficient solid tumors is being investigated across other tumor types, including HNSCC. JADE is a global, multicenter, double-blind, placebo-controlled, randomized phase 3 study evaluating the efficacy and safety of dostarlimab as post-cisplatin-based CRT sequential therapy in patients with LA unresected PD-L1-expressing HNSCC. JADE seeks to overcome the limitations of previous studies by incorporating both PD-L1 selection and solely sequential administration of dostarlimab soon after CRT.

Methods: The primary endpoint is event-free survival, with overall survival as a key secondary endpoint; safety and tolerability, pharmacokinetics, immunogenicity, biomarkers, and patient-reported outcomes will also be assessed.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT06256588.

Aims: In the absence of head-to-head comparative trials, this study aimed to compare zanubrutinib versus acalabrutinib in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) by calculating number needed to treat (NNT) to avoid one disease progression or death and associated economic impact.

Methods: A health-economic model was developed from US payer perspective using efficacy data from matching-adjusted indirect comparison for overall R/R CLL in base-case analysis, and network meta-analysis for high-risk R/R CLL in the subgroup analysis. The NNT analysis included costs of drug acquisition, adverse event management, medical resource utilization, and subsequent treatment over 24 months. Deterministic sensitivity analyses assessed model uncertainty.

Results: In the base case, zanubrutinib versus acalabrutinib avoided one progression for every 10 patients treated (NNT = 10) and one death for every 15 patients treated (NNT = 15), yielding per-patient cost savings of $7,335 over 24 months. In high-risk R/R CLL subgroup, one progression was avoided per six patients treated (NNT = 6) and one death per 18 patients treated (NNT = 18), with cost savings of $11,533 per patient. Results were robust across sensitivity analyses.

Conclusions: The NNT analysis demonstrates that treatment with zanubrutinib versus acalabrutinib is associated with more favorable clinical and economic outcomes in R/R CLL, especially in high-risk CLL patients.

Goal: To present data from published clinical trials of treatment of patients with prostate cancer with enzalutamide described in plain language and in a dashboard format available at: https://clinical-trials.dimensions.ai/enzalutamide-clinical-review/.

Rationale: Treatments that are clinically active in advanced prostate cancer may benefit patients as they are treated earlier in the disease.

Objective: To show how overall survival improves as patients are treated with enzalutamide earlier in the disease.

Aim: To review how molecular preselection and combination treatment affects overall response rate (ORR) in pediatric non-central nervous system (CNS) solid tumors treated with tyrosine kinase inhibitors (TKIs).

Methods: A systematic literature review was performed to identify studies reporting ORR (till July 2023). The review was non-registered and non-meta-analytic.

Results: 53 clinical studies involving 306 molecularly preselected patients (16 studies), 513 molecularly not preselected patients on TKI monotherapy (26 studies) and 350 molecularly not preselected patients on combination therapy (15 studies) met prespecified criteria for ORR analysis. According to the MINORS score, methodological quality was moderate to poor. Molecular preselection increased median ORR to TKI monotherapy from 0% [95% CI, 0%, 6%] to 36% [95% CI, 27%, 50%], (p = 0.001). Combination treatment increased median ORR from 0% [95% CI, 0%, 6%] to 14% [95% CI, 5%, 26%] in molecularly unselected population (p = 0.003). Comprehensive molecular characterization was absent, less than 20% of studies investigated molecular aberrations beyond the mechanism of action of tested TKI. Only few studies were terminated due to safety issues.

Conclusions: Molecular background of tumors should be taken into account when using TKIs. The current molecular pre-selection criteria are insufficient and need to be improved.

Tenosynovial giant cell tumor (TGCT) is a rare, locally invasive soft tissue tumor arising from the synovium of joints, bursa and tendon sheaths and is associated with the overexpression of the colony-stimulating factor 1 (CSF-1) gene. Pimicotinib is an orally available, highly selective and potent small molecule CSF-1 receptor (CSF-1R) inhibitor with robust efficacy and safety profile in patients with TGCT and is under development in multiple diseases. In an open-label Phase I study in patients with TGCT not amenable to surgery, pimicotinib showed superior efficacy and safety. In this article, we elucidate the rationale and study design of the multi-region Phase III MANEUVER trial (NCT05804045), which is designed to assess the efficacy and safety of pimicotinib in patients with TGCT not amenable to surgical resection in Asia, North America and Europe.

Cervical cancer screening programs reduce the number of cervical cancer cases and deaths, but the success of any screening program is dependent on high participant uptake and coverage and many European countries are observing declining cervical cancer screening coverage to below national targets. Self-collection of vaginal samples for human papillomavirus testing, also termed self-sampling, is one strategy which is being introduced to try to increase screening coverage by removing barriers to participation and it has attracted growing interest and support globally. Informed by peer-reviewed and gray literature, this narrative review starts with a case study from the Netherlands and outlines the self-collection landscape in Europe within the themes of program implementation and relative test performance. It highlights some of the current evidence gaps needed to inform policy decisions on the use of self-collection within screening programs.

Aims: This study aimed to evaluate the prognostic value of the systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) for overall survival (OS) in colorectal cancer (CRC) patients with liver metastasis after transcatheter arterial chemoembolization (TACE).

Patients and methods: A retrospective analysis of 270 CRC patients who underwent TACE was conducted. Baseline comparisons were made between survivors (n = 142) and non-survivors (n = 128) focusing on tumor size, AFP, SII, and PNI. Prognostic factors were analyzed using Cox regression, ROC curves, and Kaplan-Meier analysis.

Results: Significant differences in tumor size, AFP, SII, and PNI were found between the two groups. Multivariate Cox regression revealed that larger tumor size (HR = 1.110, p < 0.001), higher AFP (HR = 1.003, p < 0.001), and elevated SII (HR = 1.001, p < 0.001) were associated with poorer OS, while higher PNI (HR = 0.944, p < 0.001) was protective. ROC analysis yielded AUCs of 0.852 for SII and 0.876 for PNI, with a combined model improving to 0.948. Kaplan-Meier showed that high SII (≥1324.165) and low PNI (<40.915) were associated with poorer 3-year OS (p < 0.001).

Conclusions: SII and PNI are valuable prognostic indicators for OS in CRC patients post-TACE. Elevated SII and reduced PNI predict worse outcomes, and their combination enhances survival prediction.