PF‑06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin®), Both Plus Paclitaxel and Carboplatin, as First‑Line Treatment for Advanced Non‑Squamous Non‑Small‑Cell Lung Cancer: A Randomized, Double‑Blind Study

Background PF-06439535 is a bevacizumab biosimilar. We aimed to compare the efcacy and safety of PF-06439535 with that of reference bevacizumab (Avastin®) sourced from the EU (bevacizumab-EU), each with paclitaxel and carboplatin, in the frst-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC). Methods In this double-blind, parallel-group study, we recruited patients from 159 centers in 27 countries. Participants were randomized 1:1 to receive PF-06439535 plus paclitaxel and carboplatin or bevacizumab-EU plus paclitaxel and carboplatin on day 1 of each 21-day cycle for 4–6 cycles, followed by blinded monotherapy with PF-06439535 or bevacizumab-EU until disease progression, unacceptable toxicity, withdrawal of consent, or the end of the study. Randomization was stratifed by region, sex, and smoking history. The primary endpoint was objective response rate (ORR) in accordance with RECIST 1.1, based on responses achieved by week 19 and confrmed by week 25. Results Between 21 May 2015 and 14 November 2016, 719 patients were randomized to the PF-06439535 group (n = 358) or the bevacizumab-EU group (n = 361). As of data cutof for analysis of the primary endpoint (8 May 2017), 45.3% (95% confdence interval [CI] 40.01–50.57) of patients in the PF-06439535 group and 44.6% (95% CI 39.40–49.89) of patients in the bevacizumab-EU group achieved an objective response by week 19 that was confrmed by week 25. The unstratifed ORR risk ratio was 1.015 (95% CI 0.863–1.193; 90% CI 0.886–1.163), and the unstratifed ORR risk diference was 0.653% (95% CI −6.608 to 7.908); all three CIs fell within pre-specifed equivalence margins. Using fnal data after study completion (22 December 2017), no notable diferences in progression-free survival or overall survival were observed between the groups. The most frequently reported grade 3 or higher treatment-emergent adverse events were hypertension, neutropenia, and anemia. There were no clinically meaningful diferences in safety, pharmacokinetics, or immunogenicity across treatment groups. Conclusion Among patients with advanced non-squamous NSCLC, PF-06439535 demonstrated similarity to bevacizumabEU in terms of efcacy. Safety profles for the two treatments were comparable. Trial Registration ClinicalTrials.gov, NCT02364999. Funding Pfzer

Computed tomography on lung cancer screening is useful for adjuvant comorbidity diagnosis in developing countries

Purpose The aim of this study was to analyse and quantify the prevalence of six comorbidities from lung cancer screening (LCS) on computed tomography (CT) scans of patients from developing countries. Methods For this retrospective study, low-dose CT scans (n=775) were examined from patients who underwent LCS in a tertiary hospital between 2016 and 2020. An age- and sex-matched control group was obtained for comparison (n=370). Using the software, coronary artery calcification (CAC), the skeletal muscle area, interstitial lung abnormalities, emphysema, osteoporosis and hepatic steatosis were accessed. Clinical characteristics of each participant were identified. A t-test and Chi-squared test were used to examine differences between these values. Interclass correlation coefficients (ICCs) and interobserver agreement (assessed by calculating kappa coefficients) were calculated to assess the correlation of measures interpreted by two observers. p-values <0.05 were considered significant. Results One or more comorbidities were identified in 86.6% of the patients and in 40% of the controls. The most prevalent comorbidity was osteoporosis, present in 44.2% of patients and in 24.8% of controls. New diagnoses of cardiovascular disease, emphysema and osteoporosis were made in 25%, 7% and 46% of cases, respectively. The kappa coefficient for CAC was 0.906 (p<0.001). ICCs for measures of liver, spleen and bone density were 0.88, 0.93 and 0.96, respectively (p<0.001). Conclusions CT data acquired during LCS led to the identification of previously undiagnosed comorbidities. The LCS is useful to facilitate comorbidity diagnosis in developing countries, providing opportunities for its prevention and treatment