Phase i trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours

BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective secondgeneration inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS: In all, 49 patients received axitinib 5mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5mg b.i.d. with paclitaxel/carboplatin. RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia (n¼1) in the paclitaxel/carboplatin cohort and fatigue (n¼1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No gradeX3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n¼27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n¼21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. CONCLUSION: Axitinib 5mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug–drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.This study was sponsored by Pfizer Inc. Support was provided in part by National Institutes of Health grant P30 CA006927 to the Fox Chase Cancer Center. We thank the patients who participated in this study and the physicians who referred them, as well as the study coordinators and data managers, Shelley Mayfield and Carol Martins at Pfizer Inc. for support of the study conduct, and Gamal ElSawah, Pfizer Medical Affairs, for his review of the manuscript. Medical writing support was provided by Joanna Bloom, of UBC Scientific Solutions (Southport, CT, USA) and Christine Arris at ACUMED (Tytherington, UK) and was funded by Pfizer In

Baseline prognostic nutritional index and changes in pretreatment body mass index associate with immunotherapy response in patients with advanced cancer

Background Recent research suggests that baseline body mass index (BMI) is associated with response to immunotherapy. In this study, we test the hypothesis that worsening nutritional status prior to the start of immunotherapy, rather than baseline BMI, negatively impacts immunotherapy response.Methods We studied 629 patients with advanced cancer who received immune checkpoint blockade at New York University. Patients had melanoma (n=268), lung cancer (n=128) or other primary malignancies (n=233). We tested the association between BMI changes prior to the start of treatment, baseline prognostic nutritional index (PNI), baseline BMI category and multiple clinical end points including best overall response (BOR), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).Results Decreasing pretreatment BMI and low PNI were associated with worse BOR (p=0.04 and p=0.0004), ORR (p=0.01 and p=0.0005), DCR (p=0.01 and p<0.0001), PFS (p=0.02 and p=0.01) and OS (p<0.001 and p<0.001). Baseline BMI category was not significantly associated with any treatment outcomes.Conclusion Standard of care measures of worsening nutritional status more accurately associate with immunotherapy outcomes than static measurements of BMI. Future studies should focus on determining whether optimizing pretreatment nutritional status, a modifiable variable, leads to improvement in immunotherapy response

Risk factors for incomplete telehealth appointments among patients with inflammatory bowel disease

Background: The COVID-19 pandemic led to the urgent implementation of telehealth visits in inflammatory bowel disease (IBD) care; however, data assessing feasibility remain limited. Objectives: We looked to determine the completion rate of telehealth appointments for adults with IBD, as well as to evaluate demographic, clinical, and social predictors of incomplete appointments. Design: We conducted a retrospective analysis of all patients with IBD who had at least one scheduled telehealth visit at the NYU IBD Center between 1 March 2020 and 31 August 2021, with only the first scheduled telehealth appointment considered. Methods: Medical records were parsed for relevant covariables, and multivariable logistic regression was used to estimate the adjusted association between demographic factors and an incomplete telehealth appointment. Results: From 1 March 2020 to 31 August 2021, there were 2508 patients with IBD who had at least one telehealth appointment, with 1088 (43%) having Crohn’s disease (CD), 1037 (41%) having ulcerative colitis (UC), and 383 (15%) having indeterminate colitis. Of the initial telehealth visits, 519 (21%) were not completed, including 435 (20%) among patients 80 years was an independent predictor of missed telehealth appointments (adjOR: 2.92, 95% CI: 1.12–7.63) when compared to individuals aged 60–70 years. Conclusion: Patients with CD, females, and those with less social support were at higher risk for missed telehealth appointments, as were adults >80 years. Engaging older adults via telehealth, particularly those aged 60–80 years, may therefore provide an additional venue to complement in-person care

sj-docx-1-tag-10.1177_17562848231158231 – Supplemental material for Risk factors for incomplete telehealth appointments among patients with inflammatory bowel disease

Supplemental material, sj-docx-1-tag-10.1177_17562848231158231 for Risk factors for incomplete telehealth appointments among patients with inflammatory bowel disease by Katherine L. Stone, Emma Kulekofsky, David Hudesman, Samuel Kozloff, Feza Remzi, Jordan E. Axelrad, Seymour Katz, Simon J. Hong, Ariela Holmer, Mara A. McAdams-DeMarco, Dorry L. Segev, John Dodson, Aasma Shaukat and Adam S. Faye in Therapeutic Advances in Gastroenterology</p