Future oncology最新文献

Purpose: A phase I study of FOLFIRINOX3-bevacizumab (bFOLFIRINOX3)defined the RP2D for irinotecan at 70 mg/m² and showed promising activity. This phase II trial aimed to evaluate the efficacy of bFOLFIRINOX-3 in chemorefractory metastatic colorectal cancer (mCRC).

Methods: In phase II, chemorefractory mCRC were enrolled. The regimen tested consisted of bevacizumab (5 mg/kg), folinic acid(400 mg/m²), 5-fluorouracil (2400 mg/m² for 46 h), oxaliplatin (85 mg/m²) and irinotecan (70 mg/m² administered before and after infusion of 5-fluorouracil). The primary endpoint was efficacy defined by 2-month progression-free survival(PFS). Secondary endpoints included objective response, median PFS, overall survival (OS) and toxicity.

Results: 32 patients were enrolled (October 2018 to December 2022); median age 62.5 years (range 32-78). The majority had been treated with several previous lines of chemotherapy (median 3, range [1-8]). Median follow up was 12 months (range [1.5-12]). Two-month PFS was 96.9%. Best objective response rate (ORR) was 28.1%. Median PFS was 9.4 months (95%CI [6.9;11.5]) and median OS was not reached (95% [11.6; NR]). Grade 3 adverse events occurred in 81.2%; mostly diarrhea (37.5%) and neutropenia (12.5%). Grade 3 diarrhea consistently resolved after irinotecan dose reduction. The most common drug-related adverse events (all grades) were diarrhea (96.9%), fatigue (68.8%), nausea (68.7%), anemia (56.3%), peripheral neuropathy (53.4%) and thrombopenia (40.6%).

Conclusion: The combination of bFOLFIRINOX-3 yielded 2-month PFS of 96.9% and best ORR of 28.1%, and was well tolerated. These results are promising in chemotherapy refractory mCRC and provide a rationale for future randomized phase III trials.

Clinical trial registration: NCT03795311 (clinicaltrials.gov).

Aim: Multiple myeloma (MM) is a hematological malignancy associated with poor health-related quality of life (HRQoL). Safe and effective treatments for MM are limited. There is a need for real-world data to improve understanding of treatment patterns and sequencing in routine clinical practice in Japan. This study evaluated disease burden, treatment patterns, treatment sequencing, and reasons for treatment selection in patients with MM in Japan.

Methods: This analysis used survey data of hematologists or hemato-oncologists and their adult patients with MM who received active treatment in a real-world setting in Japan between September 2022 and May 2023. Treatment and retreatment patterns and data from several validated patient reported outcome tools were analyzed. Formal sample size calculations were not applicable.

Results: Fifty-one physicians provided data for 309 patients, of whom 52 completed a quality-of-life survey (median [interquartile range] overall health status by EQ-5D-3L questionnaire: 0.7 [0.6-1.0]). Of 309 patients, most (77%) of the first-line cohort received a lenalidomide-based therapy. Lenalidomide retreatment was common in patients with relapsed/refractory MM (80%).

Conclusion: Poor HRQoL and high retreatment rates indicate a need for new therapy options in patients with MM in Japan. These findings may guide healthcare policies and clinical practice in Japan.

Background: We herein retrospectively analyzed the clinicopathologic features from a large cohort of GAS patients to provide real-world evidence for optimizing the diagnosis and treatment.

Research design and methods: One hundred and fifty-seven GAS patients from three hospitals were recruited for analysis. We extracted clinical and pathologic information from patient medical records and performed regular follow-up. Logistic regression and Kaplan - Meier analyses were conducted to identify the prognostic factors.

Results: 31.2% exhibited stage I tumor, and 11.5%, 33.1%, and 24.2% manifested tumors at stages II, III, and IV, respectively. For the entire group, the median progression-free survival (PFS) and overall survival (OS) were 22 and 33 months, respectively. Multivariate analysis showed tumor stage and ovarian metastasis were predictors for PFS; and that ovarian metastasis and small tumor diameter were independent prognostic factors for OS. We determined an abnormal elevation of tumor abnormal protein (TAP) in 76% GAS patients, which could serve as a sensitive marker for tumor recurrence/metastasis.

Conclusions: We demonstrated that ovarian metastasis and FIGO stage (including tumor diameter) were independent prognostic predictors for GAS patients. Moreover, we were the first to report that TAP constituted a potent marker for GAS surveillance, thus warranting further investigation.

Background: Though efforts have been made toward standardizing access to quality cancer care in Japan, there are still geographical and institutional disparities in the level of cancer care availability. We investigated the utilization of cyclin-dependent kinase 4/6 inhibitors plus endocrine therapy (CDK4/6i+ET) as first-line (1 L) treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in Japan.

Research design and methods: This cross-sectional survey included physicians who had treated ≥3 1 L patients with HR+/HER2- ABC in the past year.

Results: Of 41,695 physicians invited, 300 were included in the analysis. The mean percentage share of CDK4/6i+ET and ET monotherapy was 38.3% and 42.2%, respectively. Common challenges facing CDK4/6i+ET prescription were adverse reaction management, prohibitive cost, and a preference for ET monotherapy for treating elderly patients. Key solutions included reducing the burden of adverse reaction management, improving financial support, and preparing educational videos for medical staff.

Conclusions: The study concluded that CDK4/6i+ET is not well established as a 1 L option in Japan as of 2022. More effective ways of creating awareness and supportive tools are needed for CDK4/6i+ET to be adopted as standard of care in Japan.

Trial registration number: UMIN000050760.

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).

Drug-eluting microsphere transarterial chemoembolization (DEM-TACE) reduces systemic exposure to chemotherapeutic drugs compared with conventional TACE but permanently occludes the embolized vessels, potentially obviating the possibility of re-treatment with TACE. Temporary embolization by resorbable BioPearl™ microspheres might facilitate subsequent re-treatments. We herein describe the trial protocol of BIOPEARL-ONE, a prospective, single-arm, multicenter, post-market clinical follow-up study. The primary objectives are technical success and safety following the use. DEM-TACE with doxorubicin-loaded BioPearl™ for unresectable hepatocellular carcinoma (HCC). The secondary objectives are tumor response, duration of response, progression-free survival, and survival rate at 18 months. Fifty patients with HCC nodules smaller than 5 cm and within the up-to-7 criteria will be enrolled.Clinical Trial Registration: NCT05911633.

What is this summary about?: In this article, we summarize results from a clinical study called LOTIS-2, in which researchers looked at patients with a type of blood cancer called diffuse large B-cell lymphoma, or DLBCL for short. Patients received the drug loncastuximab tesirine, or Lonca for short, which targets a marker on the surface of tumor cells called CD19.Patient information from the LOTIS-2 study, other studies of Lonca, and information from scientific publications was used to develop a quantitative systems pharmacology (QSP) model, which can predict how Lonca works in the body. The goal was to use the QSP model to see if CD19 levels can predict tumor size changes after Lonca treatment and if Lonca can still work to treat DLBCL when CD19 levels are very low. The prior LOTIS-1 and LOTIS-2 trials demonstrated an acceptable safety profile for Lonca, and therefore the current study did not evaluate safety data.

What were the results?: Researchers used immunohistochemistry, a common technique to evaluate CD19 expression. They found that there was no association between patients who responded to Lonca treatment and levels of CD19 on their tumor cells. Some patients with low or even undetectable levels of CD19 on their tumor cells had observable decreases in tumor size after Lonca treatment.

What do the results of the study mean?: While Lonca uses the CD19 target to find and destroy cancer cells, Lonca does not require a large amount of CD19 to kill tumor cells. These results mean that Lonca may be an effective treatment for patients with DLBCL, even if CD19 expression in tumors is undetectable by immunohistochemistry.