Future oncology最新文献

Background: The purpose of this study was to identify barriers to physicians' NGS use and preferred strategies to alleviate these barriers.

Research design and methods: A cross-sectional online survey link was sent to a sample of US oncologists/hematologists, surgeons, and pathologists identified through a panel. The survey collected data, from October-December 2020, on barriers to NGS testing and potential strategies.

Results: Two hundred physicians participated (mean age: 46.2 years; 65% male; 80% White, mean years in clinical practice: 13.7). Despite the use of NGS testing by all physicians, 99.5% reported concerns/barriers. Reimbursement challenges were the most cited reason (87.5%), followed by lack of knowledge of NGS testing methodologies (81.0%), and lack of clinical utility evidence (80.0%). The most common reimbursement challenge was prior authorizations for NGS testing (72.0%), followed by knowledge of new fee codes for reimbursement or corresponding therapy (68.0%), and paperwork/administrative duties (67.5%). Surgeons were more likely to encounter challenges in using NGS testing than other physicians.

Conclusions: The results highlight the barriers reported by oncologists/hematologists, pathologists, and surgeons, which may impact the evolving role of NGS in the context of the overall management of cancer patients.

Aims: To assess real-world progression-free survival (rwPFS) and time to next treatment (rwTTNT) among patients with epithelial ovarian cancer (EOC) who received first-line maintenance (1LM) niraparib monotherapy.

Patients & methods: In this US-nationwide, electronic health record-derived, deidentified database study, eligible patients with EOC initiated 1LM niraparib monotherapy (1 January 2017-1 December 2022) following first-line platinum-based chemotherapy. Median rwPFS and rwTTNT were estimated with Kaplan-Meier methodology overall and in a homologous recombination-deficient (HRd) subgroup (further stratified as BRCA wild-type [BRCAwt] or BRCA-mutated [BRCAm]).

Results: Observed median rwPFS was 11.4 (95% CI, 10.1-12.7) months overall (N = 560), 18.2 (95% CI, 13.9-24.2) months for the HRd subgroup (n = 144), and 25.4 (95% CI, 15.9-not reached) and 14.2 (95% CI, 8.6-18.6) months for HRd patients with BRCAm and BRCAwt tumors, respectively. Observed median rwTTNT was 12.4 (95% CI, 11.5-13.8) months overall, 19.6 (95% CI, 14.9-23.9) months for the HRd subgroup, and 24.9 (95% CI, 16.0-not reached) and 15.1 (95% CI, 10.3-19.8) months for HRd patients with BRCAm and BRCAwt tumors, respectively.

Conclusions: The real-world observed median rwPFS and rwTTNT were longer for patients with EOC who received 1LM niraparib monotherapy in the HRd subgroup (specifically for the BRCAm subgroup).

Aims: This systematic review summarizes real-world clinical outcomes and economic burden of first-line FOLFIRINOX (FFX)/modified FFX (mFFX) and nab-paclitaxel plus gemcitabine (GnP) in metastatic pancreatic ductal adenocarcinoma in the US.

Methods: Embase and MEDLINE were searched for materials published since 2014; citations were reviewed in a two-step process. Included studies were qualitatively synthesized.

Results: Searches yielded 2,528 citations; 29 were included (17 clinical studies/12 economic studies). In 9/17 clinical studies, median overall survival (mOS) ranged from 4.7 months to 11.4 months for FFX/mFFX, with the unweighted median of the estimates within this range being 9.2 months; for GnP mOS ranged from 3.6 to 9.8 months, and the unweighted median of the estimates was 6.9 months. In 8/17 studies, grade 3/4 anemia, neutropenia, and thrombocytopenia were the most commonly reported adverse events. Across economic burden studies, total costs were similar between the 2 groups. Outpatient, supportive care, and granulocyte colony-stimulating factor costs were higher for the FFX generic regimen, and chemotherapy costs were higher for the GnP branded regimen.

Conclusions: Real-world OS in FFX- and GnP-treated populations was shorter than that in clinical trials, and total costs of FFX and GnP were similar, but with differences in cost components.

BI 1703880, a novel STimulator of INterferon Genes (STING) agonist, has demonstrated preclinical antitumor activity. As STING activation can upregulate programmed death ligand 1 and human leukocyte antigen in tumor cells, a combination of BI 1703880 and an anti-programmed cell death protein 1-antibody, such as ezabenlimab, may improve efficacy. This first-in-human phase Ia study (NCT05471856) is evaluating BI 1703880 plus ezabenlimab in patients with advanced solid tumors. The study utilizes an innovative lead-in design; all patients receive BI 1703880 monotherapy in Cycle 1 and combination therapy from Cycle 2. The primary endpoint is dose-limiting toxicities during the maximum tolerated dose evaluation period. Results will inform the future development of BI 1703880 for treatment of metastatic or recurrent malignancies.Clinical Trial number: NCT05471856.

What is this summary about?: Researchers combined information from three separate phase 1 and 2 clinical trials, including over 400 people who had one of 33 different cancer types and who all received futibatinib in their clinical trial. This type of study is called a pooled analysis. Futibatinib is taken orally (by mouth) as a tablet and works by reducing the activity of a group of proteins called fibroblast growth factor receptors (FGFRs). FGFRs drive the growth of some cancers, especially cancer cells with changes in FGFR genes that make the proteins more active. Researchers wanted to look at how common some side effects were in people treated with futibatinib, how soon the side effects happened after taking futibatinib, and how they could be managed. Researchers also wanted to provide recommendations to other health care professionals on how to manage these side effects in people with cancer.

What were the results?: In this analysis, the researchers focused on side effects that they had seen in previously completed trials of futibatinib. Overall, futibatinib was safe and tolerable. Most people (82%) had a high phosphate level in their blood (hyperphosphatemia), 27% had nail disorders, 27% had liver side effects (changes in liver-related laboratory tests), 19% had a sore mouth (stomatitis), 13% had hand-foot syndrome (palmar-plantar erythrodysesthesia syndrome), 9% had a rash, 8% developed changes in the back of the eye (retinal disorders), and 4% of people developed cataracts. Most side effects were mild/moderate and reversible. The median time it took from starting treatment to experiencing a severe side effect ranged from 9 days (hyperphosphatemia) to 125 days (cataracts). Some side effects tended to occur early, while others developed later. Only 2% of people stopped taking futibatinib due to treatment-related side effects, and futibatinib caused no deaths.

What do the results mean?: The side effects from taking futibatinib were manageable and similar in people with different types of cancer. To fully understand the safety of futibatinib, researchers will need to look at what side effects are reported in people taking futibatinib over a longer time in the real-world setting (outside of clinical trials).

Aims: Limited head-to-head data exist for daratumumab plus pomalidomide and dexamethasone (DPd) and non-pomalidomide-containing triplet regimens to treat relapsed/refractory multiple myeloma (RRMM). This study conducted population-adjusted indirect comparisons of overall survival (OS) for DPd vs. daratumumab, carfilzomib, and dexamethasone (DKd) and daratumumab, bortezomib, and dexamethasone (DVd).

Materials & methods: A systematic literature review was performed via searches of databases and relevant conference proceedings. Both simulated treatment comparison (STC) and matching-adjusted indirect comparison (MAIC) were used to adjust for between-trial differences.

Results: Seven randomized controlled trials were identified, five of which were subsequently excluded from the indirect treatment comparison during feasibility assessment. A consistent OS benefit was observed for DPd vs. DKd and DVd for patients with RRMM, using both STC and MAIC methods.

Conclusions: The findings of this study support the use of DPd over DKd and DVd for the treatment of patients with early RRMM.

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.

Aim: Cancers lacking standard screening (LSS) options account for approximately 70% of cancer-related deaths due to late-stage diagnosis. Circulating tumor DNA (ctDNA) is a promising biomarker for multi-cancer early detection. We previously developed SPOT-MAS, a multimodal ctDNA-based assay analyzing methylation and fragmentomic profiles, effective in detecting common cancers (breast, colorectal, liver, lung and gastric). This study extends the analysis to five LSS cancers: endometrial, esophageal, head and neck, ovarian and pancreatic.Methods: SPOT-MAS was applied to profile cfDNA methylation and fragmentomic patterns in 739 healthy individuals and 135 LSS cancer patients.Results: We identified 347 differentially methylated regions and observed genome-wide hypomethylation across all five LSS cancers. Esophageal and head and neck cancers showed an enrichment of short cfDNA fragments (<150 bp). Eleven 4-mer end motifs were consistently altered in cfDNA fragments across all LSS cancers. Many significant signatures were consistent with previous observations in common cancers. Notably, SPOT-MAS achieved 96.2% specificity and 74.8% overall sensitivity, with a lower sensitivity of 60.7% in early-stage cancers.Conclusion: This proof-of-concept study demonstrates that SPOT-MAS a non-invasive test trained on five common cancer types, could detect a number of LSS cancer cases, potentially complementing existing screening programs.

What is this summary about?: This summary includes information from the ARCHES and ENZAMET follow-up studies. Both studies looked at enzalutamide treatment for people with metastatic hormone-sensitive prostate cancer (known as mHSPC). In ARCHES, researchers compared the medications enzalutamide + androgen deprivation therapy (known as ADT) with placebo + ADT. In ENZAMET, researchers compared enzalutamide + ADT with standard treatment + ADT. Some people in ENZAMET also took enzalutamide with docetaxel (a chemotherapy treatment). In both studies, researchers wanted to find out if enzalutamide helps people with mHSPC live longer.

What are the key takeaways?: In both studies, researchers found that people with mHSPC who took enzalutamide lived longer than people who did not. People who took enzalutamide also lived longer without their cancer getting worse. The results were mostly similar in groups of people dependingon when and where their cancer was found. Researchers did not find any new safety concerns.

What were the main conclusions?: People with mHSPC may benefit from long-term treatment with enzalutamide + ADT. They may also benefit from taking enzalutamide with other treatments, like docetaxel. It may be better for people with mHSPC to have enzalutamide treatment before their cancer gets worse, rather than waiting. These people and their doctors should carefully consider the benefits and risks of each treatment to make a joint decision for treating mHSPC.Clinical Trial Registration: NCT02677896 (ARCHES), NCT02446405 (ENZAMET) (ClinicalTrials.gov).