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.

Background: Avoiding unnecessary dose reductions is important for patients with advanced breast cancer (ABC) receiving trastuzumab deruxtecan (T-DXd). Nausea and vomiting, the most common adverse events of T-DXd, frequently necessitate dose reductions, which may impact treatment benefit.

Methods: This retrospective exploratory study investigated the impact of triple antiemetic regimen (TAR) prophylaxis on T-DXd dose preservation over time. Data from 143 human epidermal growth factor receptor 2 (HER2)-positive or HER2-low ABC patients who received ≥2 T-DXd cycles were stratified based on TAR use in the first cycle. TAR included an NK₁ receptor antagonist, a 5-HT₃ receptor antagonist (or fixed netupitant/palonosetron combination), and dexamethasone.

Results: Patients receiving TAR in the first cycle were significantly less likely to require T-DXd dose reductions in subsequent cycles than the non-TAR group (31.3% vs. 66.7%, P = 0.033). The lowest T-DXd dose relative to initial dose for each patient was significantly higher in the TAR group than in the non-TAR group (100% vs. 80.6%, P = 0.001). There was a trend toward a longer median time to T-DXd dose reduction in the TAR group (15.7 vs. 3.9 months; P = 0.183).

Conclusion: These findings suggest that upfront TAR may help maintain the dosing of T-DXd in patients with HER2-positive or HER2-low ABC.

Lorlatinib is a third-generation tyrosine kinase inhibitor approved for first- and second-line treatment of ALK-positive advanced non-small cell lung cancer. The CROWN study demonstrated that first-line lorlatinib significantly improves progression-free survival and intracranial control compared to crizotinib, with sustained benefits observed over a follow-up period of up to 5 years. As lorlatinib is associated with a distinct adverse event (AE) profile, we aim to analyze lorlatinib's safety profile, focusing on AEs incidence, severity, timing and management. A comprehensive safety management framework is also outlined to address lorlatinib-associated toxicity, drawing on evidence from the literature and the clinical expertise of an Italian expert panel. The most frequent AEs associated with lorlatinib are hypercholesterolemia and hypertriglyceridemia, which emerge early after treatment initiation. The 5-year analysis of the CROWN study revealed minimal changes in most AE rates over time. Pharmacological and non-pharmacological approaches effectively resolved most AEs; lorlatinib dose reduction did not affect its efficacy. The proposed safety management framework emphasizes patient preparation and regular monitoring to predict AE occurrence, indicating AE-specific interventions, mitigation strategies and multidisciplinary collaboration to optimize outcomes. Lorlatinib's toxicity appears generally predictable and manageable; the safety framework offers pragmatic guidance to clinicians for appropriate management in clinical practice.

Aim: Programmed death (ligand) 1 inhibitors (e.g., avelumab, pembrolizumab, and retifanlimab) are first-line treatment options for patients with locally advanced or metastatic Merkel cell carcinoma (MCC). In the absence of comparative and randomized trials, we aimed to systematically identify and synthesize real-world evidence (RWE) on the effectiveness and safety of immunotherapies in patients with advanced MCC.

Methods & materials: MEDLINE and Embase searches were conducted for observational RWE studies in locally advanced or metastatic MCC from January 2017 to December 2023. Avelumab was the only immunotherapy with sufficient data for analysis. Landmark 12-month overall survival (OS) and progression-free survival (PFS) were assessed by meta-analysis.

Results: Screening of 1731 records identified 37 publications eligible for inclusion (16 unique studies), of which eight were included in the meta-analysis. In line with results from the JAVELIN Merkel 200 trial, pooled 12-month OS rates of 77.7% in stage III and 63.0% in stage IV MCC and 12-month PFS rates of 53.3% and 39.3%, respectively, were estimated. Although safety data were insufficient for meta-analysis, two retrospective studies reported lower adverse event rates than JAVELIN Merkel 200.

Conclusions: The results of this study support broader use of avelumab in advanced MCC.

Aims: The study team investigated the relative efficacy of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) versus positron emission tomography (PET)-guided doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) among previously untreated adults with advanced Hodgkin lymphoma via matching-adjusted indirect comparison (MAIC).

Materials & methods: A systematic literature review identified ECHELON-1 (A+AVD), RATHL, and SWOG S0816 as feasible trials referencing a targeted comparator (PET-guided ABVD). Effect modifiers/prognostic variables were identified by clinical expert opinion and Cox regression using long-term ECHELON-1 individual patient-level data. Weighted Cox regressions generated hazard ratios (HR) and 95% confidence intervals (CI) representing A+AVD versus PET-guided ABVD relative treatment effect on overall survival (OS) and progression-free survival (PFS).

Results: OS improved significantly with A+AVD versus PET-guided ABVD (HR [95% CI] 0.48 [0.32, 0.73], p < 0.001 [RATHL]; 0.49 [0.26, 0.92], p = 0.043 [SWOG S0816]). PFS significantly favored A+AVD over PET-guided ABVD in both trial comparisons. While the proportional hazards assumption did not hold for these comparisons, 8-year restricted mean survival time and piecewise Cox regression results aligned with the main results.

Conclusion: MAIC results indicated durable A+AVD treatment benefits in adults with newly diagnosed advanced Hodgkin lymphoma versus PET-guided regimens evaluated in RATHL and SWOG S0816.

Aims: To explore the prognostic value of the combined SII-PNI (Systemic Immune-Inflammation Index + Prognostic Nutritional Index) in cholangiocarcinoma (CCA) patients.

Methods: Retrospective analysis of 149 CCA patients' clinical data was conducted, with the SII-PNI scoring system used to assess its prognostic impact.

Results: Chi-square analysis showed SII-PNI correlated with CEA and CA19-9 (p < 0.05). Kaplan-Meier curves revealed significant progression-free survival (PFS) differences among SII-PNI groups (p < 0.005). Cox univariate analysis identified AST, CA19-9, and CEA as PFS prognostic factors (p < 0.05), but only SII-PNI was an independent factor in multivariate analysis (p < 0.005).

Conclusion: SII-PNI (integrating inflammation and nutrition) effectively predicts CCA's PFS (HR = 1.51, p < 0.005), outperforming conventional biomarkers like CA19-9. Its cost-effectiveness supports CCA risk stratification. However, SII-PNI-based dynamic treatment response monitoring is unvalidated (retrospective limitation) and needs prospective trials; no intensified treatment recommendations are made.

Aims: Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) have relapsed or refractory (R/R) disease after first-line treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, and outcomes are poor after hematopoietic stem cell transplantation failure. CheckMate 436 (NCT02581631) was a phase 1/2 study to evaluate the efficacy and safety of nivolumab, a PD-1/PD-L1 inhibitor, plus brentuximab vedotin (BV) for the treatment of R/R non-Hodgkin lymphoma.

Materials and methods: Adult patients received nivolumab plus BV in 3-week cycles. The primary endpoint was overall response rate (ORR). Here, we report the results from the R/R DLBCL cohort (n = 42).

Results: With a median follow-up of 7.7 months, the ORR was 28.6% (n = 12), and 7.1% (n = 3) of patients achieved a complete response. Median duration of response (95% CI) was 3.6 (1.2-36.5) months. All patients experienced an adverse event (AE), most commonly diarrhea (n = 20, 47.6%). Grade 3/4 and 5 AEs occurred in 24 (57.1%) and 4 (9.5%) patients, respectively. Any-grade treatment-related AEs occurred in 35 (83.3%) patients. No new safety signals were identified.

Conclusions: Overall, the efficacy data from CheckMate 436 do not support the use of nivolumab plus BV for the treatment of R/R DLBCL.

Background: Durvalumab was initially approved for stage III unresectable non-small cell lung cancer (NSCLC) post-concurrent chemoradiation at 10 mg/kg every two weeks, and starting in November 2020, at 1500 mg every four weeks (Q4W). Real-world evidence is limited on durvalumab Q4W dosing utilization and discontinuation, especially in community-based oncology settings.

Methods: In this retrospective cohort, we examined patients with stage III unresectable NSCLC who initiated durvalumab between 3 January 2019 and 12/31/2021, including those who switched to Q4W dosing or received Q4W dosing only, with follow-up until durvalumab discontinuation, health plan disenrollment, death, or study's end.

Results: Of the 102 patients (mean age: 71 years; 46.1% female; 46.1% non-White; 80.4% formerly smoked), 40 switched to Q4W dosing, and 62 received Q4W dosing only. Median duration of treatment (DoT) was 10.0 months overall and 7.5 months for Q4W only. About one-third of patients receiving Q4W dosing completed treatment. Discontinuation occurred in 51.5% of all patients and 65.5% receiving Q4W dosing only. The most common discontinuation reasons were disease progression (17.7%) and pneumonitis (14.7%).

Conclusion: In this diverse community-based cohort, Q4W dosing outcomes, including DoT and completion rate, were comparable to other real-world studies with Q2W dosing and the PACIFIC and PACIFIC-R trials.