Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non-Small Cell Lung Cancer: The NRG-LU001 Phase 2 Randomized Clinical Trial.

IMPORTANCE: Non-small cell lung cancer (NSCLC) has relatively poor outcomes. Metformin has significant data supporting its use as an antineoplastic agent. OBJECTIVE: To compare chemoradiation alone vs chemoradiation and metformin in stage III NSCLC. DESIGN, SETTING, AND PARTICIPANTS: The NRG-LU001 randomized clinical trial was an open-label, phase 2 study conducted from August 24, 2014, to December 15, 2016. Patients without diabetes who were diagnosed with unresectable stage III NSCLC were stratified by performance status, histology, and stage. The setting was international and multi-institutional. This study examined prespecified endpoints, and data were analyzed on an intent-to-treat basis. Data were analyzed from February 25, 2019, to March 6, 2020. INTERVENTIONS: Chemoradiation and consolidation chemotherapy with or without metformin. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year progression-free survival (PFS), designed to detect 15% improvement in 1-year PFS from 50% to 65% (hazard ratio [HR], 0.622). Secondary end points included overall survival, time to local-regional recurrence, time to distant metastasis, and toxicity per Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: A total of 170 patients were enrolled, with 167 eligible patients analyzed after exclusions (median age, 64 years [interquartile range, 58-72 years]; 97 men [58.1%]; 137 White patients [82.0%]), with 81 in the control group and 86 in the metformin group. Median follow-up was 27.7 months (range, 0.03-47.21 months) among living patients. One-year PFS rates were 60.4% (95% CI, 48.5%-70.4%) in the control group and 51.3% (95% CI, 39.8%-61.7%) in the metformin group (HR, 1.15; 95% CI, 0.77-1.73; P = .24). Clinical stage was the only factor significantly associated with PFS on multivariable analysis (HR, 1.79; 95% CI, 1.19-2.69; P = .005). One-year overall survival was 80.2% (95% CI, 69.3%-87.6%) in the control group and 80.8% (95% CI, 70.2%-87.9%) in the metformin group. There were no significant differences in local-regional recurrence or distant metastasis at 1 or 2 years. No significant difference in adverse events was observed between treatment groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the addition of metformin to concurrent chemoradiation was well tolerated but did not improve survival among patients with unresectable stage III NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02186847.

Pre-transplant consolidation chemotherapy may not improve outcomes after reduced intensity conditioning hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission.

The role consolidation chemotherapy prior to reduced-intensity (RIC) HCT is unclear. We reviewed 60 consecutive patients with AML in CR1 undergoing RIC HCT at the University of Minnesota and evaluated outcomes based on exposure to pre-transplant consolidation chemotherapy. The two year incidence of relapse and the probability of overall survival were similar between those who did and did not receive consolidation chemotherapy. The 2 year incidence of transplant-related mortality was slightly higher in those who did not receive consolidation and correlated with a higher HCT comorbidity index (HCT-CI) in that cohort. Our data suggest that exposure to consolidation chemotherapy prior to RIC HCT may not improve post-transplant outcomes for patients with AML in CR1.

Epigenetic approaches in the treatment of myelodysplastic syndromes: clinical utility of azacitidine.

Myelodysplastic syndromes (MDS) are a varied group of diseases leading to significant morbidity and mortality. Therapy of MDS has been difficult, with supportive cares used to ameliorate symptoms, and hematopoietic stem cell transplantation the only curative option. Agents, such as the cytidine analog azacitidine, exert an effect on DNA methyltransferase leading to a reduction in DNA methylation, a process thought to be key to the pathogenesis of MDS. Recently, azacitidine has been shown to prolong survival and improve quality of life in patients with MDS, while maintaining a favorable adverse effect profile. This review highlights the scientific rationale for the use of azacitidine in addition to its application in current clinical practice for patients with MDS.