Future oncology最新文献

Aims: To investigate real-world treatment patterns and outcomes among patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) who initiated first-line palbociclib-fulvestrant.

Patients & methods: Retrospective observational study of iKnowMed electronic health records among patients who initiated first-line palbociclib-fulvestrant between 1 February 2016 and 31 December 2019 and were followed through 30 June 2020. Demographic, clinical, and treatment characteristics were evaluated descriptively. Endpoints including real-world progression-free survival, overall survival, time to chemotherapy, real-world duration of therapy, and time to next treatment were assessed using Kaplan-Meier methods from first-line treatment initiation.

Results: 317 patients were included (median age 67.3 years, 90.5% post-menopausal, 36.9% bone-only disease, 15.9 months median follow-up). Among those with prior adjuvant treatment (n = 269), 66.2% (n = 178) had disease-free intervals less than 12 months. Median real-world progression-free survival was 19.6 months (95% CI 15.2-23.6).

Conclusions: These results suggest favorable real-world clinical outcomes associated with first-line palbociclib-fulvestrant among patients with HR+/HER2- mBC. (clinical trial registration: NCT04498481).

What is this summary about?: Advanced prostate cancer is a cancer that began in the prostate (a part of the male body) and has spread to other parts of the body. This is a review of two clinical research studies of patients with advanced prostate cancer who were treated with relugolix combination therapy. Relugolix is a medicine taken by mouth that lowers a male sex hormone, called testosterone. Relugolix is sometimes combined with other medicines such as novel hormonal therapies (NHTs) or chemotherapy to treat advanced prostate cancer. In one study, patients were treated with relugolix combined with an NHT (abiraterone or apalutamide). In a second study, patients were treated with relugolix combined with an NHT (enzalutamide) or chemotherapy (docetaxel). Researchers wanted to understand what possible side effects may happen due to taking these medicines together as prescribed. They also wanted to see if relugolix combination therapy worked to lower testosterone in the same way as relugolix taken alone.

What are the key takeaways?: Researchers found that most of the side effects of relugolix combined with an NHT or chemotherapy were mild or moderate. Side effects of relugolix combination therapy were similar to the side effects of the medicines when taken alone. However, patients who received relugolix with enzalutamide or docetaxel were more likely to have a serious side effect compared with patients who received relugolix taken alone. Testosterone stayed below 50 nanograms per deciliter (known as castration levels) for patients who received relugolix with NHT or chemotherapy.

What were the main conclusions reported by the researchers?: Patients who receive relugolix combination therapy generally experience mild or moderate side effects, rather than serious side effects. No new safety issues were found during these studies. Patients maintained low testosterone levels. Patients and their doctors should discuss the benefits and possible harms of relugolix combination therapy to treat advanced prostate cancer.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is prognostic of poor survival for patients with non-small cell lung cancer (NSCLC). KRAS G12C mutations occur in 13% of NSCLC cases and despite the frequency of this mutation, advances in drug development against KRAS have historically been impeded due to the extremely high affinity of KRAS for guanosine triphosphate (GTP) and the lack of a binding pocket on the surface of KRAS that is suitable for drug binding. Sotorasib, a first-in-class, highly selective KRAS G12C inhibitor overcomes this issue by irreversibly binding in the switch-II pocket. Sotorasib was granted accelerated FDA approval for the treatment of KRASG12C-mutated locally advanced/metastatic NSCLC who have received at least one prior systemic therapy. This review summarizes the pharmacology, clinical efficacy, adverse effects, and clinical considerations of sotorasib.

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).