Future oncology最新文献

Background: Approvals of Bruton's tyrosine kinase inhibitors (BTKis) and other novel agents have changed the Mantle Cell Lymphoma (MCL) treatment paradigm, necessitating assessment of contemporaneous, real-world (rw) treatment and outcomes by line of therapy (LOT).

Methods: Patients diagnosed with MCL on or after 1 January 2012 who initiated first-line (1 L) treatment in the COTA database were eligible, excluding those with concurrent primaries, history of hematologic malignancies, clinical trial participation, or missing/imprecise key dates. Rw time to next treatment (rwTTNT) and overall survival (rwOS) were evaluated using the Kaplan-Meier method from LOT start (index).

Results: Of 499 patients, most were ≥ 50 years (94.8%), male (71.5%), treated in the community (58.7%), and diagnosed with stage III/IV disease (91.2%). The most common 1 L regimen was bendamustine+rituximab (BR)±R maintenance (12.6%/23.0%, respectively). Fifty (10.0%) patients received 1 L autologous stem cell transplant. One hundred and seventy-three patients (34.7%) received 2 L, of which 72 (41.6% of 2 L) received 3 L, of which 29 (40.3% of 3 L) received 4 L +. BTKi monotherapy was the most frequently administered therapy in 2 L (26.0%).Median rwTTNT and rwOS from 1 L to 4 L were 36.8-3.2 and 86.2-8.7 months, respectively.

Conclusions: Outcomes of patients who received 2 L+ for MCL remain poor, highlighting unmet need in the contemporary treatment paradigm.

Aims: This study aims to evaluate the diagnostic potential of [¹⁸F]TFB PET/CT for detecting pre-operative lymph node metastases and predicting [¹³¹I] therapy response in differentiated thyroid cancer (DTC).

Methods: This prospective, multicenter phase-2 clinical trial includes adult patients with DTC and pathologically confirmed cervical lymph node metastases scheduled for thyroidectomy and lymph node dissection (Group 1) and patients with recurrent or persistent DTC scheduled for radioiodine therapy (Group 2). [¹⁸F]TFB PET/CT will be compared to current imaging modalities and post-therapy scintigraphy. Primary outcomes include optimal imaging time points, sensitivity, specificity, SUV_max, and TBR_max for lymph node metastases and suspected lesions. Secondary outcomes involve [¹⁸F]TFB kinetics, NIS expression correlation, and safety profiles. In conclusion, [¹⁸F]TFB PET/CT holds the potential for enhancing pre-operative lymph node metastasis detection and predicting [¹³¹I] therapy response, potentially improving surgical and therapeutic outcomes for DTC patients.

Aim: To understand the real-world use of abemaciclib in older patients (≥65 years) with HR+, HER2- metastatic breast cancer (MBC) in Japan.

Methods: This study retrospectively analyzed a Japanese administrative claims database for patients with HR+, HER2- MBC who received abemaciclib as the first CDK4/6 inhibitor (CDK4/6i) from November 2018 to May 2023. Patient characteristics and treatment patterns were summarized. Median time to discontinuation (mTTD) and chemotherapy-free survival (CSF) was estimated using Kaplan - Meier method.

Results: Among 3,699 abemaciclib-treated patients with HR+, HER2- MBC, 1,681 (45.4%) were ≥65 years old. Among these, abemaciclib + fulvestrant (55.0%) was the most common regimen. The mTTD (95% CI) of first abemaciclib therapy was 12.8 months (11.4-13.6). The overall mTTD (95% CI) with all the BC drugs after starting abemaciclib was 40.2 months (37.0-44.0). The median (95% CI) CFS after starting abemaciclib was 34.8 months (30.2-39.5). Among 1,149 older patients who discontinued the abemaciclib therapy, 897 (78.1%) patients received subsequent treatment. The most common first subsequent therapy was the endocrine therapy + CDK4/6i regimen (34.9%).

Conclusion: This study indicated that abemaciclib regimens were feasible for older patients with HR+, HER2- MBC in Japan.

Real-world evidence (RWE) is increasingly used to support product approvals and label expansions, as well as clinical and payer decision-making. Various tools (e.g. frameworks, checklists) have been developed to help inform and assess the robustness and quality of real-world study design and reporting. This targeted review provides a practical guide for leveraging these tools to increase awareness and utility for decision-makers. A pre-defined search strategy was applied to identify articles from PubMed. Articles published from 1 January 2020, through 4 October 2024 were included and reviewed to identify relevant tools aimed at assessing RWE study planning, reporting, or quality assessment. Key information regarding each was extracted and summarized including strengths, limitations, and included domains. 119 articles were initially identified, of which 15 were included after screening, referencing a total of 17 tools. These 17 tools varied in format and structure, ranging from detailed guidelines and templates to checklists and questionnaires. Utility and application of the tools identified in this targeted review vary across the evaluation of study planning, reporting, and quality. Selection of the appropriate tool depends on several factors including intended purpose of the tool, intended real-world study design, and the availability of study documentation.

Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. B7 homolog 3 (B7-H3) is minimally expressed in normal tissues but highly expressed in SCLC. Ifinatamab deruxtecan (I-DXd), a B7-H3-directed antibody-drug conjugate, has demonstrated promising efficacy and a manageable safety profile in various tumours, including SCLC. IDeate-Lung02 is a global, randomized, open-label Phase 3 study of ~540 patients with relapsed SCLC. Adults with one prior line of platinum-based systemic therapy, ECOG performance status 0-1, and ≥1 measurable lesion (per RECIST 1.1) are eligible for study participation. Patients with asymptomatic untreated or previously treated brain metastases may participate. Patients are randomized 1:1 to receive I-DXd 12 mg/kg intravenously every 3 weeks or treatment of physician's choice (topotecan, amrubicin, or lurbinectedin). Dual primary endpoints are objective response rate (ORR) by blinded independent central review (BICR) and overall survival. Secondary endpoints include ORR by investigator; progression-free survival, duration of response, disease control rate, and time to response, all by BICR and investigator; patient-reported outcomes; and safety. IDeate-Lung02 will ascertain whether I-DXd treatment after only one prior line of systemic treatment improves outcomes for patients with relapsed SCLC compared with topotecan, amrubicin, or lurbinectedin.Clinical Trial Registration: NCT06203210.

Aims: Ovarian cancer (OC) is a prevalent gynecological malignancy with high mortality due to its asymptomatic progression and advanced stage at diagnosis. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is beneficial for patients unsuitable for primary debulking surgery (PDS). Effective markers for assessing NACT outcomes could significantly aid clinical decision-making and personalized treatment strategies.

Patients & methods: In this retrospective study, we examined fibrinolytic markers, including D-dimer, fibrinogen (FIB), and fibrinogen degradation products (FDP), among 167 OC patients and 110 healthy controls. Plasma levels of these markers were measured before and after four NACT cycles in OC patients, and receiver operating characteristic (ROC) analysis was conducted to evaluate their diagnostic and predictive value.

Results: OC patients exhibited significantly elevated baseline levels of D-dimer, FIB, and FDP compared to healthy controls. Post-NACT measurements showed that responders had a substantial decrease in these markers, while non-responders showed minimal changes. ROC analysis confirmed the diagnostic accuracy of D-dimer, FIB, and FDP, with high sensitivity and specificity for predicting NACT effectiveness.

Conclusion: D-dimer, FIB, and FDP are elevated in OC patients and demonstrate a potential role as noninvasive markers for assessing NACT efficacy, offering valuable insights for treatment planning.

Aim: To evaluate the safety and effectiveness of ruxolitinib in patients with myelofibrosis (MF) in Japan.

Methods: A multicenter, observational study of patients who received ruxolitinib for MF from July 2014.

Results: Of 892 patients (mean age: 70 years, 45.9% primary MF, ruxolitinib treatment median duration, 541.0 days), 67.7% had adverse drug reactions (ADRs) and 31.5% had serious ADRs. The most frequent ADRs were anemia and decreased platelet count. Incidences of ADRs by time of onset were 57.7%, 20.3%, 14.4%, 11.1%, 11.3%, 9.0%, and 1.8% from the treatment initiation to Day 182, and every 6 months thereafter until Day 1,093 or later, respectively. ADRs of special interest included myelosuppression (46.8%), infections (17.6%), hepatic impairment (13.5%), hemorrhagic events (10.2%), cardiac failure (2.5%), interstitial lung disease (1.5%), malignancy (1.4%) and tuberculosis (0.5%). Incidences of common ADRs were similar between patients with hepatic or renal impairment and patients without hepatic or renal impairment. At 6 months, spleen responses and symptom improvement were observed in 26.2% and 52.0% of patients, respectively. Median overall survival was not reached.

Conclusion: In a real-world setting in Japan, ruxolitinib demonstrated a reasonable degree of effectiveness with no new safety concerns. Results were similar to those from clinical trials.