Search

Objectives: Erythropoiesis-stimulating agents (ESAs) remain first-choice to treat symptomatic anemia and delay transfusion dependence in most patients with lower-risk myelodysplastic syndromes (MDS) without del(5q). Deferasirox increased erythroid responses in some lower-risk MDS patients in clinical trials, and adding low-dose deferasirox to ESA treatment may further improve erythroid response. Methods: KALLISTO (NCT01868477) was a randomized, open-l abel, multicenter, phase II study. Lower-risk MDS patients received deferasirox at 10 mg/kg/d (dispersible tablets) or 7 mg/kg/d (film-coated tablets) plus erythropoietin (n = 11), or erythropoietin alone (n = 12) for 24 weeks. The primary endpoint was the between-group difference in erythroid response within 12 weeks. Results: Erythroid response occurred in 27.3% of patients receiving deferasirox plus erythropoietin vs 41.7% of patients receiving erythropoietin alone within 12 weeks (difference 14.4%; 95% CI -24.0, 48.16). Within 24 weeks, the hematologic response rate was 27.3% with deferasirox plus erythropoietin vs 50% with erythropoietin alone, and hematologic improvement rates were 45.5% vs 100%. Deferasirox plus erythropoietin was generally well tolerated. Conclusions: In this small pilot study, combining low-dose deferasirox with erythropoietin did not improve erythroid response. It remains of interest to investigate early chelation approaches with even lower deferasirox doses plus erythropoietin in lower-risk MDS patients before the onset of transfusion dependence. [ABSTRACT FROM AUTHOR]

Anti-PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma (EGA), but long-term survival remains limited. Herein, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti-PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison to a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti-CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease. The 12-month overall survival (OS) showed no statistical difference between the arms, with 57% OS (95% CI: 41%-71%) in the Ipi arm and 70% OS (95% CI: 54%-82%) in the FOLFOX arm. Crossing of the survival curves indicated a potential long-term benefit for some patients within the Ipi arm, but early progressors in the Ipi arm underlined the need for biomarker-guided strategies to optimize treatment selection. To this end, metabolomic and cytokine analysis demonstrated elevated levels of normetanephrine, cortisol, and interleukin 6 (IL-6) in immunotherapy-unresponsive patients in the Ipi arm, suggesting a role for systemic inflammatory stress in modulating antitumor immune responses. Patients with this signature also showed an increased neutrophil-to-lymphocyte ratio (NLR) that persisted in the Ipi arm, but not in the FOLFOX arm, and strongly correlated with survival. Furthermore, a low NLR characterized patients benefiting from immune- and targeted therapy without the need for additional chemotherapy. This data suggests that patient selection based on inflammatory stress-driven immune changes could help to customize first-line treatment in patients with advanced HER2-positive EGA to potentially improve long-term survival.

Purpose: Surrogate end points are commonly used to estimate treatment efficacy in clinical studies of chronic lymphocytic leukemia (CLL). This patient- and trial-level analysis describes the correlation between progression-free survival (PFS) and minimal residual disease (MRD) with overall survival (OS) in first-line trials for CLL., Patients and Methods: First, patient-level correlation was confirmed using source data from 12 frontline German CLL Study Group (GCLLSG)-trials. Additionally, a joint-frailty copula model was fitted to validate correlation in the setting of targeted therapies (TT). Second, a meta-analysis of first-line phase III trials in CLL from 2008 to 2024 was performed. Treatment effect correlation was quantified from seven GCLLSG and nine published trials, using hazard ratios (HRs) for time-to-event and odds ratios for binary end points., Results: The GCLLSG analysis set comprised 4,237 patients. Patient-level correlation for PFS/OS was strong with Spearman Rho >0.9. The joint-frailty copula indicated a weak correlation for chemotherapy/chemoimmunotherapy (C/CIT) with a tau of 0.52 (95% CI, 0.49 to 0.55) while the correlation was strong for TT (tau, 0.91 [95% CI, 0.89 to 0.93). The meta-analysis set contained a total of 8,065 patients including 5,198 (64%) patients treated with C/CIT and 2,867 (36%) treated with TT. Treatment-effect correlation of the HRs for PFS and OS was R = 0.75 (95% CI, 0.74 to 0.76, R 2 = 0.56) while correlation of end-of-treatment MRD with PFS and OS was R = 0.88 (95% CI, -0.87 to 0.89; R 2 = 0.78) and 0.71 (95% CI, 0.69 to 0.73; R 2 = 0.5), respectively., Conclusion: Patient-level correlation was confirmed in the setting of TTs while treatment-effect correlation between PFS and OS remains uncertain. MRD response status showed a high treatment-effect correlation with PFS but not OS, with the caveat of a limited number of randomized trials with available MRD data.

Few data exist on health-related quality of life (QoL) in patients with metastatic pancreatic cancer (mPC) receiving first-line chemotherapy (Awad L ZE, Mesbah M Boston, MA. Applying survival data methodology to analyze quality of life data, in Mesbah M, Cole BF, Ting Lee M-L (eds): Statistical Methods for Quality of Life Studies: Design, Measurements and Analysis. Kluwer Academic Publishers 2002). The QOLIXANE study is a prospective, noninterventional, multicenter substudy of the Platform for Outcome, Quality of Life and Translational Research on Pancreatic Cancer (PARAGON) registry, which evaluated QoL in patients with mPC receiving first-line gemcitabine and nab-paclitaxel chemotherapy in real-life setting. QoL was prospectively measured via EORTC QLQ-C30 questionnaires at baseline and every month thereafter. Therapy and efficacy parameters were prospectively collected. Main objectives were the rate of patients without deterioration of Global Health Status/QoL (GHS/QoL) at 3 and 6 months. Six hundred patients were enrolled in 95 German study sites. Median progression-free survival was 5.9 months (95% confidence interval [CI], 5.2-6.3). Median overall survival (OS) was 8.9 months (95% CI, 7.9-10.2), while median time to deterioration of GHS/QoL was 4.7 months (95% CI, 4.0-5.6). With a baseline GHS/QoL score of 46 (SD, 22.8), baseline QoL of the patients was severely impaired, in most cases due to loss in role functioning and fatigue. In the Kaplan-Meier analysis, 61% and 41% of patients had maintained GHS/QoL after 3 and 6 months, respectively. However, in the QoL response analysis, 35% and 19% of patients had maintained (improved or stable) GHS/QoL after 3 and 6 months, respectively, while 14% and 9% had deteriorated GHS/QoL with the remaining patients being nonevaluable. In the Cox regression analysis, GHS/QoL scores strongly predicted survival with a hazard ratio of 0.86 (P < .0001). Patients with mPC have poor QoL at baseline that deteriorates within a median of 4.7 months. Treatment with gemcitabine and nab-paclitaxel is associated with maintained QoL in relevant proportions of patients. However, overall, results remain poor, reflecting the aggressive nature of the disease., (© 2020 Union for International Cancer Control.)