Strain Elastography Fat-to-Lesion Index Is Associated with Mammography BI-RADS Grading, Biopsy, and Molecular Phenotype in Breast Cancer.

Breast cancer (BC) affects millions of women worldwide, causing over 500,000 deaths annually. It is the leading cause of cancer mortality in women, with 70% of deaths occurring in developing countries. Elastography, which evaluates tissue stiffness, is a promising real-time minimally invasive technique for BC diagnosis. This study assessed strain elastography (SE) and the fat-to-lesion (F/L) index for BC diagnosis. This prospective study included 216 women who underwent SE, ultrasound, mammography, and breast biopsy (108 malignant, 108 benign). Three expert radiologists performed imaging and biopsies. Mean F/L index was 3.70 ± 2.57 for benign biopsies and 18.10 ± 17.01 for malignant. We developed two predictive models: a logistic regression model with AUC 0.893, 79.63% sensitivity, 87.62% specificity, 86.9% positive predictive value (+PV), and 80.7% negative predictive value (-PV); and a neural network with AUC 0.902, 80.56% sensitivity, 88.57% specificity, 87.9% +PV, and 81.6% -PV. The optimal Youden F/L index cutoff was >5.76, with 84.26% sensitivity and specificity. The F/L index positively correlated with BI-RADS (Spearman's r = 0.073, p < 0.001) and differed among molecular subtypes (Kruskal-Wallis, p = 0.002). SE complements mammography for BC diagnosis. With adequate predictive capacity, SE is fast, minimally invasive, and useful when mammography is contraindicated.

Pembrolizumab With or Without Lenvatinib for First-Line Metastatic NSCLC With Programmed Cell Death-Ligand 1 Tumor Proportion Score of at least 1% (LEAP-007): A Randomized, Double-Blind, Phase 3 Trial.

INTRODUCTION: Lenvatinib plus pembrolizumab was found to have antitumor activity and acceptable safety in previously treated metastatic NSCLC. We evaluated first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab in metastatic NSCLC in the LEAP-007 study (NCT03829332/NCT04676412). METHODS: Patients with previously untreated stage IV NSCLC with programmed cell death-ligand 1 tumor proportion score of at least 1% without targetable EGFR/ROS1/ALK aberrations were randomized 1:1 to lenvatinib 20 mg or placebo once daily; all patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary end points were progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival (OS). We report results from a prespecified nonbinding futility analysis of OS performed at the fourth independent data and safety monitoring committee review (futility bound: one-sided p < 0.4960). RESULTS: A total of 623 patients were randomized. At median follow-up of 15.9 months, median (95% confidence interval [CI]) OS was 14.1 (11.4‒19.0) months in the lenvatinib plus pembrolizumab group versus 16.4 (12.6‒20.6) months in the placebo plus pembrolizumab group (hazard ratio = 1.10 [95% CI: 0.87‒1.39], p = 0.79744 [futility criterion met]). Median (95% CI) PFS was 6.6 (6.1‒8.2) months versus 4.2 (4.1‒6.2) months, respectively (hazard ratio = 0.78 [95% CI: 0.64‒0.95]). Grade 3 to 5 treatment-related adverse events occurred in 57.9% of patients (179 of 309) versus 24.4% (76 of 312). Per data and safety monitoring committee recommendation, the study was unblinded and lenvatinib and placebo were discontinued. CONCLUSIONS: Lenvatinib plus pembrolizumab did not have a favorable benefit‒risk profile versus placebo plus pembrolizumab. Pembrolizumab monotherapy remains an approved treatment option in many regions for first-line metastatic NSCLC with programmed cell death-ligand 1 tumor proportion score of at least 1% without EGFR/ALK alterations.

First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1.

INTRODUCTION: In CheckMate 227 (NCT02477826), patients with treatment-naive stage IV or recurrent NSCLC and 1% or greater tumor programmed death ligand 1 expression had significantly improved overall survival with nivolumab plus ipilimumab versus chemotherapy. We present the patient-reported outcomes (PROs). METHODS: Patients (N = 1189) were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy. PROs were exploratory. Changes in Lung Cancer Symptom Scale (LCSS) average symptom burden index, LCSS 3-item global index, EQ-5D visual analog scale (VAS), and EQ-5D utility index were analyzed descriptively. Mixed-effect model repeated measures and time-to-first deterioration and improvement analyses were conducted. RESULTS: PRO completion rates were generally greater than 80%. On-treatment improvements from baseline in LCSS measures of symptom burden and global health status with nivolumab plus ipilimumab generally met or exceeded the minimal important difference (smallest clinically meaningful change) from weeks 24 and 30, respectively; improvements with chemotherapy generally remained below the minimal important difference. Mean on-treatment EQ-5D VAS scores for both treatments approached the U.K. population norm at week 24, remaining so throughout the treatment period. Mixed-effect model repeated measures analyses revealed numerically greater improvements from baseline with nivolumab plus ipilimumab versus chemotherapy across LCSS average symptom burden index and 3-item global index, and EQ-5D VAS and utility index. Nivolumab plus ipilimumab had delayed time-to-first deterioration (hazard ratio [95% confidence interval] 0.74 [0.56 to 0.98]) and a trend for more rapid time-to-first improvement (1.24 [0.98 to 1.59]) versus chemotherapy. CONCLUSIONS: Nivolumab plus ipilimumab revealed delayed deterioration and numerical improvement in symptoms and health-related quality of life versus chemotherapy in patients with advanced NSCLC and 1% or greater programmed death ligand 1 expression.

Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: In an early-phase study involving patients with advanced non-small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with tumors that expressed programmed death ligand 1 (PD-L1). Data are needed to assess the long-term benefit of nivolumab plus ipilimumab in patients with NSCLC. METHODS: In this open-label, phase 3 trial, we randomly assigned patients with stage IV or recurrent NSCLC and a PD-L1 expression level of 1% or more in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. The patients who had a PD-L1 expression level of less than 1% were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. All the patients had received no previous chemotherapy. The primary end point reported here was overall survival with nivolumab plus ipilimumab as compared with chemotherapy in patients with a PD-L1 expression level of 1% or more. RESULTS: Among the patients with a PD-L1 expression level of 1% or more, the median duration of overall survival was 17.1 months (95% confidence interval [CI], 15.0 to 20.1) with nivolumab plus ipilimumab and 14.9 months (95% CI, 12.7 to 16.7) with chemotherapy (P = 0.007), with 2-year overall survival rates of 40.0% and 32.8%, respectively. The median duration of response was 23.2 months with nivolumab plus ipilimumab and 6.2 months with chemotherapy. The overall survival benefit was also observed in patients with a PD-L1 expression level of less than 1%, with a median duration of 17.2 months (95% CI, 12.8 to 22.0) with nivolumab plus ipilimumab and 12.2 months (95% CI, 9.2 to 14.3) with chemotherapy. Among all the patients in the trial, the median duration of overall survival was 17.1 months (95% CI, 15.2 to 19.9) with nivolumab plus ipilimumab and 13.9 months (95% CI, 12.2 to 15.1) with chemotherapy. The percentage of patients with grade 3 or 4 treatment-related adverse events in the overall population was 32.8% with nivolumab plus ipilimumab and 36.0% with chemotherapy. CONCLUSIONS: First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level. No new safety concerns emerged with longer follow-up. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 227 ClinicalTrials.gov number, NCT02477826.).