Exploratory analysis of the association of depth of response and survival in patients with metastatic non-small-cell lung cancer treated with a targeted therapy or immunotherapy

Abstract

Our analysis suggests a greater DepOR is associated with longer PFS and OS for patients receiving ALKi or anti-PD1 Ab. Overall, this suggests that DepOR may provide an additional outcome measure for clinical trials, and may allow better comparisons of treatment activity.

The Value of Early Depth of Response in Predicting Long-Term Outcome in EGFR-Mutant Lung Cancer

“…In these studies, patients have been categorized into CR and PR vs SD or progressive disease. 16,19,22 However, in two studies examining the degree of tumor shrinkage quantitatively, DR was not associated with improved survival outcomes, consistent with our finding. 19,20 Furthermore, the methodological approach used in some of these studies was also criticized for not accounting for guarantee-time bias.…”

Association between depth of response and survival in patients with advanced‐stage non–small cell lung cancer treated with first‐line chemotherapy

“…In patients with NSCLC, DpR has been associated with improved outcomes for patients treated with targeted therapy or immune checkpoint blockers (ICBs). In a pooled analysis of 660 patients from 4 randomized controlled trials, including 2 studies with an anaplastic kinase inhibitor and 2 with a programmed cell death 1 antibody, there was a correlation between DpR and survival for both subsets of patients . Nevertheless, DpR was not associated with PFS or OS in 2 studies involving patients with epidermal growth factor receptor ( EGFR ) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) .…”

“…In a pooled analysis of 660 patients from 4 randomized controlled trials, including 2 studies with an anaplastic kinase inhibitor and 2 with a programmed cell death 1 antibody, there was a correlation between DpR and survival for both subsets of patients. 10 Nevertheless, DpR was not associated with PFS or OS in 2 studies involving patients with epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs). 11,12 Furthermore, in a pooled analysis involving patients with EGFR mutations enrolled in 5 randomized Cancer July 15, 2019 clinical trials comparing EGFR TKIs with chemotherapy, no association was found between DpR at 6 or 12 weeks and long-term survival among patients treated with either an EGFR TKI or chemotherapy.…”

An Analysis of Recent FDA Oncology Scientific Publications

“…The topics of these publications are informed by issues identified during regulatory review. FDA oncology staff are in a unique position to articulate important research questions based on review work across cancer types and product classes and have access to oncology clinical trial data submitted by multiple sponsors for meta‐analyses and data to study patterns of regulatory submissions over time . Recent FDA oncology publications have addressed a variety of regulatory science topics, including the following: Describing new methods to design clinical trials for regulatory submissions such as master protocols , patient‐reported outcome tools , expansion cohorts , and tumor‐agnostic drug development . Exploring clinical trial endpoints . Investigating approaches to ensure that clinical trials are representative of the general population such as expanding eligibility criteria , understanding representation of diverse populations , and using real world data (e.g., electronic health record data) to inform regulatory actions . …”

“…The topics of these publications are informed by issues identified during regulatory review. FDA oncology staff are in a unique position to articulate important research questions based on review work across cancer types and product classes and have access to oncology clinical trial data submitted by multiple sponsors for meta-analyses [2][3][4][5] and data to study patterns of regulatory submissions over time [6]. Recent FDA oncology publications have addressed a variety of regulatory science topics, including the following:…”