Benefit of axicabtagene ciloleucel versus chemoimmunotherapy in older patients and/or patients with poor ECOG performance status with relapsed or refractory large B-cell lymphoma after 2 or more lines of prior therapy.

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients treated with CIT for R/R LBCL after ≥2 lines of prior therapy were included from SCHOLAR-1 (an international, multicohort, retrospective study). After propensity score matching, at a median follow-up of 24 months for patients receiving axi-cel and 60 months for patients receiving CIT, 12-month overall survival rates were 62% and 28%, respectively (hazard ratio, 0.30 [95% CI, 0.24-0.37]). Objective response rate (ORR) was 76% (complete response [CR] rate 58%) in patients receiving axi-cel versus 28% (CR rate 16%) for those receiving CIT. A 57% difference in ORR (55% difference in CR rate) favoring axi-cel over CIT was observed among patients aged ≥65 years. Increased magnitude of benefit in response rates for axi-cel versus CIT was also observed among patients with ECOG PS = 2. These findings further support the broader use of axi-cel in older patients and patients with ECOG PS = 2 with R/R LBCL.

Defining Comprehensive Disease Control for Use as a Treatment Target for Ulcerative Colitis in Clinical Practice: International Delphi Consensus Recommendations.

BACKGROUND AND AIMS: Treatment of ulcerative colitis [UC] requires a patient-centric definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative, we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process. METHODS: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before Round 3. Consensus was met if ≥67% of the panel agreed. Statements without consensus in Rounds 1 and 2 were revised or discarded after Round 3. RESULTS: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials [rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use] with additional patient-reported symptoms [bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance]. The panel agreed on scoring systems and thresholds for many aspects. CONCLUSIONS: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multicomponent tool and will adopt comprehensive disease control as a treatment target in clinical practice and trials.

Association between event-free survival and overall survival after neoadjuvant treatment for non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: We wanted to evaluate if event-free survival (EFS) is a reliable surrogate for overall survival (OS) in patients with resectable non-small cell lung cancer (r-NSCLC) receiving neoadjuvant therapy. We conducted a systematic literature review and meta-analysis to investigate the statistical association between EFS and OS. RESEARCH DESIGN AND METHODS: Electronic databases were searched on 30 July 2021 to identify sources reporting both EFS and OS data in patients with stage I-IIIB r-NSCLC receiving neoadjuvant therapy. Correlation and regression analyses evaluated the association between the effect of treatment on EFS and OS using log-hazard ratios (HRs). Sources in which the entire population had epidermal growth factor receptor mutations were excluded from the analyses. RESULTS: We identified 74 sources, of which 8 reported EFS and OS HRs from randomized controlled trials. Based on these, we found a positive linear correlation and a strong association between EFS and OS log-HRs (weighted Pearson's correlation coefficient r = 0.864; 95% confidence interval 0.809-0.992; P = 0.006; random-effects meta-regression, R2 = 0.777). CONCLUSIONS: We found a strong association between treatment effects for EFS and OS, indicating that improvements in EFS are likely to be predictive of improvements in OS. EFS may therefore be a reliable surrogate for OS after neoadjuvant therapy in r-NSCLC.

Real-world use of bevacizumab in metastatic colorectal, metastatic breast, advanced ovarian and cervical cancer: a systematic literature review.

AIM: This review aims to assist physicians and payers in assessing the efficacy and safety of bevacizumab in real-world clinical practice by identifying evidence on the comparative effectiveness and safety of bevacizumab in its most frequent indications. Materials & methods: In a systematic review of the published literature, electronic databases (Embase®, MEDLINE® and the Cochrane Library) were searched in May 2016 and updated in January 2017; 20 scientific congresses were searched in 2014-2017. RESULTS: Of 61 included publications, 49, eight, four and 0 concerned metastatic colorectal cancer, metastatic breast cancer, advanced ovarian cancer and cervical cancer, respectively. Fifteen publications (metastatic colorectal cancer) reported on factors predictive of response to therapy. CONCLUSION: Effectiveness findings from real-world studies broadly supported results from registration studies.

Systematic Review and Meta-analysis of Short- versus Long-Acting Granulocyte Colony-Stimulating Factors for Reduction of Chemotherapy-Induced Febrile Neutropenia.

INTRODUCTION: Short- and long-acting granulocyte-colony stimulating factors (G-CSFs) are approved for the reduction of febrile neutropenia. A systematic literature review was performed to identify randomized controlled trials (RCTs) and non-RCTs reporting the use of G-CSFs following chemotherapy treatment. METHODS: Medline®/Medline in-process, Embase®, and the Cochrane Library were searched for studies published between January 2003 and June 2016. A hand-search of relevant conference proceedings was conducted for meetings held between 2012 and 2016. Eligible studies were restricted to those reporting a direct, head-to-head comparison of short- versus long-acting G-CSFs for reduction of chemotherapy-induced febrile neutropenia. Risk-of-bias assessments were performed for full publications only. RESULTS: The search strategy yielded 4044 articles for electronic screening. Thirty-six publications were evaluated for the meta-analysis: 11 of 12 RCTs and 2 of 24 non-RCTs administered doses of the short-acting G-CSF filgrastim for ≥ 7 days. In RCT studies, there was no statistically significant difference in outcomes of interest between short- and long-acting G-CSFs. In non-RCTs, the overall risk was lower with long-acting G-CSF than with short-acting G-CSF for incidence of febrile neutropenia [overall relative risk (RR) = 0.67, P  = 0.023], hospitalizations (overall RR = 0.68, P  < 0.05), and chemotherapy dose delays (overall RR = 0.68, P  = 0.020). CONCLUSIONS: Overall, the weight of evidence from RCTs indicates little difference in efficacy between the short- and long-acting G-CSFs if dosed according to recommended guidelines. There is some evidence for greater efficacy for long-acting G-CSFs in non-RCTs, which may be a result of under-dosing of short-acting G-CSFs in general practice in real-world usage. FUNDING: Hospira Inc, which was acquired by Pfizer Inc in September 2015, and Pfizer Inc.