Consolidation treatment of durvalumab after chemoradiation in real‐world patients with stage III unresectable non‐small cell lung cancer

Abstract

Background: Treatment for stage III non-small cell lung cancer (NSCLC) of unresectable disease mainly involves concurrent chemoradiation (CRT). Post-CRT consolidation treatment with durvalumab is a major therapeutic advance that provides survival benefit in this group of patients. However, the performance of this treatment strategy remains to be studied in a real-world setting. Methods: A total of 31 patients who had disease control post-CRT were included in the durvalumab early access program (EAP) as an intent-to-treat cohort and retrospectively reviewed for post-CRT progression-free survival (PFS) and time to metastatic disease or death (TMDD). The neutrophil-to-lymphocyte ratio (NLR) at the initiation of durvalumab was analyzed in 29 patients. Results: The median time from the completion of concurrent CRT to the initiation of durvalumb was 2.8 months. The objective response was 25.8% and the 12 month PFS and TMDD-free rate were 56.4% and 66.9%, respectively. The low NLR patients showed a significantly longer post-CRT PFS (not reach vs. 12.0 months [95% CI: 5.5-not estimable]; P = 0.040; the hazard ratio for disease progression or death, 0.23 [95% CI: 0.05-1.00]; P = 0.048) and the 12 month post-CRT PFS rate (82.5 vs. 42.6%). The post-CRT TMDD (not reach vs. 12.6 months, [95% CI: 10.8-not estimable]; P = 0.010; the hazard ratio for distant metastasis or death, 0.11 [95% CI: 0.01-0.88]; P = 0.037) and 12 month post-CRT TMDD-free rate (90.9 vs. 57.1%) were also significantly higher in the low NLR patients. Conclusions: Durvalumab consolidation treatment in real-world patients showed substantial efficacy and the correlation with the NLR level warrants further investigation.

Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable, locally advanced NSCLC patients

“…Pneumonitis (15%, 4 patients) was the predominant toxicity resulting in treatment interruption. All these findings are in close accordance with recently published data [14][15][16][17][18][19][20][21][22][23][24].…”

Safety and Efficacy of PD‐1/PD‐L1 inhibitors combined with radiotherapy in patients with non‐small‐cell lung cancer: a systematic review and meta‐analysis

“…AEs were defined using the National Cancer Institute‐Common Terminology Criteria for Adverse Events (NCI‐CTCAE), version 4.0. One study used the NCI‐CTCAE, version 5.0 31 and another used the NCI‐CTCAE, version 3.0 7 . The included studies primarily reported the total AE rates and immune‐related or radiation pneumonitis rates associated with combination therapy using PD‐1/PD‐L1 inhibitors and RT.…”

“…Analysis of pooled data from 66 prospective trials of ICIs (which included 25,836 patients) showed that the incidence of hematological toxicity and pneumonitis associated with combined radio‐immunotherapy may be slightly higher than that of RT alone, whereas the incidence of colitis, hepatitis, and myocarditis may be slightly lower, although these differences were statistically nonsignificant. We observed that some of the included single‐arm studies reported a relatively high incidence of AEs or mild pneumonitis 29,31,33,36 . The method of administration of combined radio‐immunotherapy 33 and the small sample size of some of the included studies (which is likely to have introduced a risk of bias) could have contributed to these results.…”

Efficacy and safety of immune checkpoint inhibitor consolidation after chemoradiation in patients of Asian ethnicity with unresectable stage III non‐small cell lung cancer: Chinese multicenter report and literature review

“…A Japanese retrospective analysis of 108 patients found that rates of grade 1, 2, and 3 pneumonitis were 58%, 26%, and 1% with a V20 constraint of 35% 23 . Another analysis of 31 patients found that pneumonitis occurred in 17.2% of all patients, and was of at least grade 3 in 6.9% of these patients 24 . In Table 4 we have summarized the incidence of pneumonitis associated with ICI consolidation therapy in Asian patients in different studies.…”

“…23 Another analysis of 31 patients found that pneumonitis occurred in 17.2% of all patients, and was of at least grade 3 in 6.9% of these patients. 24 In Table 4 we have summarized the incidence of pneumonitis associated with ICI consolidation therapy in Asian patients in different studies. These analyses indicate that the pneumonitis rates range from 17.2% to 85% (pooled rate: 67.1%), with grade 3 or higher pneumonitis occurring in 0%-14.3% of patients (pooled rate: 4.4%, Table 4).…”