Current status and progress of concurrent chemoradiotherapy in patients with locally advanced non‐small cell lung cancer prior to the approval of durvalumab

Abstract

Background: The standard treatment for patients with unresectable locally advanced (LA) non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT). Consolidation therapy with durvalumab after CRT demonstrated survival benefits and was approved in Japan in July 2018. The use of immune checkpoint inhibitors (ICIs) is entering routine oncological practice, and here we investigate the feasibility of concurrent CRT for LA-NSCLC patients based on the PACIFIC criteria. Methods: We performed a retrospective study to evaluate the feasibility and efficacy of concurrent CRT prior to the approval of durvalumab. We assessed consecutive patients with LA-NSCLC treated with CRT between January 2012 and June 2018. Results: We analyzed a total of 108 consecutive patients who received radical thoracic radiotherapy and concurrent platinum-based chemotherapy. Of those patients, 105 (97%) completed the planned radiotherapy. Radiation pneumonitis was observed in 93 patients (85%), with a median of 130 days (range: 41-317 days) from the initiation of radiation to the onset of the complication. Among the patients, 74 (69%) were considered eligible for consolidation therapy with durvalumab. The overall response rate was 64%, and the two-year survival rate was 63%. Patients who received an ICI after relapse were associated with significantly better survival than those who did not receive an ICI (two-year survival rate: 87% vs. 41%, respectively; P = 0.001). Conclusions: Prior to the approval of durvalumab, the clinical application of ICIs improved the outcome of patients with relapsed NSCLC after CRT for LA-NSCLC. The management of radiation pneumonitis remains a challenge following the approval of durvalumab.

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

“…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.…”

“…These results thus suggest that ICI consolidation therapy is safe and feasible in Chinese patients. 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 .…”

<p>Low Prognostic Nutritional Index Predicts Poor Clinical Outcomes in Patients with Stage IIIB Non-small-cell Lung Carcinoma Undergoing Chemoradiotherapy</p>

“…[39][40][41] Recently, durvalumab, a selective IgG1 monoclonal antibody which blocks PD-L1 binding to PD-1 and CD-80 allowing T cells to recognize and kill tumor cells, has been approved as the adjuvant standard of care after CRT with Level 1 proof for treatment of unresectable NSCLC. 42 To our best information, to date, no study particularly addressed the prognostic significance of PNI in NSCLC patients treated with the standard CRT followed by durvalumab or other immunotherapeutics. Nevertheless, neutrophil to lymphocyte ratio which is another inflammation index has been addressed as a prognostic indicator in some limited studies, [43][44][45] and a meta-analysis.…”

Construction of the optimization prognostic model based on differentially expressed immune genes of lung adenocarcinoma

“…Most patients’ overall survival is less than 5 years whom were diagnosed at advanced stage [ 26 ]. Existing treatments extend the survival of part of patients with lung adenocarcinoma, but the overall curative effect is not so good, especially in the advanced cases [ 27 , 28 ]. The shortage of effective prognostic biomarkers to guide therapy is one of the reasons for the poor prognosis [ 29 ].…”