Prediction of Disease Progression to Upfront Pembrolizumab Monotherapy in Advanced Non-Small-Cell Lung Cancer with High PD-L1 Expression Using Baseline CT Disease Quantification and Smoking Pack Years

Abstract

Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress. In 138 eligible patients from our institution, we retrospectively collected their baseline variables, including baseline CT findings (primary lung tumor size and metastatic site), smoking pack years, performance status, tumor pathology, and demographics. The treatment response was assessed via RECIST 1.1 using the baseline and first follow-up CT. Associations between the baseline variables and progressive disease (PD) were tested by logistic regression analyses. The results showed 46/138 patients had PD. The baseline CT “number of involved organs” by metastasis and smoking pack years were independently associated with PD (p < 0.05), and the ROC analysis showed a good performance of the model that integrated these variables in predicting PD (AUC: 0.79). This pilot study suggests that the combination of baseline CT disease and smoking PY can identify who may progress on pembrolizumab monotherapy and can potentially facilitate decision-making for the optimal first-line treatment in the high PD-L1 cohort.

The opportunities and challenges of perioperative therapy of localized non-small cell lung cancer—thoughts from the KEYNOTE-671 trial

“…These findings highlight the favorable EFS observed with pembrolizumab treatment, and are consistent with the observations from most of perioperative trials including CheckMate-816, IMpower010, and KEYNOTE-091 ( 1 , 3 , 4 ) confirming the efficacy of ICIs in reducing disease recurrence or progression. The KN671 trial demonstrated clear EFS benefit across various subgroups with the exception of never smokers and patients with programmed cell death ligand 1 (PD-L1) <1%, who may not achieve as durable of a response compared to current or former smokers, and patients with positive PD-L1 expression, in line with previous findings ( 11 , 12 ). Regarding overall survival (OS), the estimated OS at 24 months was 80.9% in the pembrolizumab group and 77.6% in the placebo group with a P=0.02, which did not meet the significance criterion based on predetermined statistical thresholds.…”