Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non–Small-Cell Lung Cancer (MYSTIC)

Abstract

We investigated the impact of durvalumab ± tremelimumab versus chemotherapy on patient-reported symptoms, functioning, and global health status/quality of life in the phase 3 MYSTIC trial of metastatic nonsmall-cell lung cancer in patients with tumor cell programmed cell death ligand 1 expression ≥ 25%. Durvalumab ± tremelimumab reduced symptom burden and improved times to deterioration, suggesting there were no detrimental effects with treatment. Background: The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic nonsmall-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs). Patients and Methods: Treatmentnaïve patients were randomized (1:1:1) to dur valumab, dur valumab + tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests. Results: There were no between-arm differences in

Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors for Advanced Non-small Cell Lung Cancer: A Network Meta-Analysis of Randomized Clinical Trials

“…The literature retrieval strategy is shown in (Figure 3A). The pneumonitis involved seven different treatment regimens (pembrolizumab, nivolumab, durvalumab, atezolizumab, pembrolizumab + platinum, atezolizumab + platinum, nivolumab + ipilimumab and platinum-based chemotherapy) in 11 studies (Reck et al, 2016;Corey et al, 2016;Carbone et al, 2017;Paz-Ares et al, 2018;Gandhi et al, 2018;Barlesi et al, 2018;West et al, 2019;Tony et al, 2019;Naiyer et al, 2020;Jotte et al, 2020;Roy et al, 2020) (Figure3B). Colitis and hepatitis involved six different treatment regimens (pembrolizumab, nivolumab, durvalumab, atezolizumab, pembrolizumab + platinum, atezolizumab + platinum and platinum-based chemotherapy) in 10 studies (Corey et al, 2016;Reck et al, 2016;Carbone et al, 2017;Barlesi et al, 2018;Gandhi et al, 2018;Paz-Ares et al, 2018;Tony et al, 2019;West et al, 2019;Jotte et al, 2020;Naiyer et al, 2020) (Figure3C).…”

“…After removing duplicates, 352 studies were used to filter through screening titles and abstracts, then 39 studies were assessed by screening full text. Finally, 12 RCTs ( Reck et al, 2016 ; Corey et al, 2016 ; Carbone et al, 2017 ; Barlesi et al, 2018 ; Paz-Ares et al, 2018 ; Gandhi et al, 2018 ; Hellmann et al, 2019 ; Tony et al, 2019 ; West et al, 2019 ; Roy et al, 2020 ; Jotte et al, 2020 ; Naiyer et al, 2020 ) including 8,453 patients with advanced NSCLC were considered eligible for inclusion in this network meta-analysis. The literature retrieval strategy is shown in Figure 2 .…”

“…The inconsistency test conducted that p values＞0.05 indicated there was significant consistency between direct and indirect results of all comparisons, and then the sensitivity analysis indicated stable results (Supplementary figure S4A-E). (Corey et al, 2016;Reck et al, 2016;Carbone et al, 2017;Barlesi et al, 2018;Gandhi et al, 2018;Paz-Ares et al, 2018;Hellmann et al, 2019;Tony et al, 2019; West et al, 2019;Jotte et al, 2020;Naiyer et al, 2020;Roy et al, 2020). These RCTs suggested that the efficacy and treatmentrelated side effects of ICI + chemotherapy, ICI alone or dual ICIs were better than chemotherapy alone.…”

“…Data on irAEs from published studies and Clinicaltrials.gov from 2015 to 2020 were collected. Finally, 12 head-to-head phase II and III RCTs (Corey et al, 2016;Reck et al, 2016;Carbone et al, 2017;Barlesi et al, 2018;Gandhi et al, 2018;Paz-Ares et al, 2018;Hellmann et al, 2019;Tony et al, 2019;West et al, 2019;Jotte et al, 2020;Naiyer et al, 2020;Roy et al, 2020)including 8,453 patients with advanced NSCLC were included in this network meta-analysis. Notably, this NMA concluded that for dermatologic irAEs, colitis, endocrine irAEs, pneumonitis and hepatitis, ICI-based therapy showed a higher incidence of irAEs than platinum-based chemotherapy.…”

“…However CTLA-4 inhibitors can inhibit the molecule CTLA-4, allowing T cells to proliferate and attack tumor cells. Data from a series of randomized clinical trials suggest that ICIs alone or in combination as first-line treatment for advanced NSCLC patients provides better clinical benefits and fewer side effects than conventional platinum-based chemotherapy ( Corey et al, 2016 ; Reck et al, 2016 ; Carbone et al, 2017 ; Barlesi et al, 2018 ; Gandhi et al, 2018 ; Paz-Ares et al, 2018 ; Hellmann et al, 2019 ; Tony et al, 2019 ; West et al, 2019 ; Jotte et al, 2020 ; Naiyer et al, 2020 ; Roy et al, 2020 ). However, ICIs enhance self immune functions against cancer cells through a unique mechanism that blocks negative regulators expressed on immune or tumor cells, while yielding higher rates of irAEs than platinum-based chemotherapy ( Remon et al, 2020 ).…”