Real‐world outcomes of chemoradiotherapy for unresectable Stage III non‐small cell lung cancer: The SOLUTION study

Abstract

There are limited real‐world data on the treatment practices, outcomes, and safety of chemoradiotherapy (CRT) alone in potential candidates for immune checkpoint inhibitors (ICI) for unresectable non‐small cell lung cancer (NSCLC). In this study, we analyzed the safety and efficacy of CRT in patients who underwent CRT and would satisfy the key eligibility criteria for maintenance therapy with durvalumab (eg, no progression after CRT) in real‐world settings (m‐sub) for unresectable Stage III NSCLC between 1 January 2013 and 31 December 2015 at 12 sites in Japan. The m‐sub comprised 214 patients with a median follow‐up of 31.6 months (range 1.9‐65.8 months). Median overall survival (OS) and progression‐free survival (PFS) from completing CRT were 36.4 months (95% confidence interval [CI] 28.1 months to not reached) and 9.5 months (95% CI 7.7‐11.7 months), respectively. Consolidation chemotherapy did not influence OS or PFS. Median PFS was 16.9 vs 9.1 months in patients with vs without epidermal growth factor receptor (EGFR) mutations, with PFS rates of ~20% at 3‐4 years. Pneumonitis was the most common adverse event (according to MedDRA version 21.0J), and about half of events were grade 1. Pneumonitis mostly occurred 10‐24 weeks after starting CRT, peaking at 18‐20 weeks. Esophagitis and dermatitis generally occurred from 0 to 4 weeks, peaking at 2‐4 weeks after starting CRT. Pericarditis was rare and occurred sporadically. In conclusion, the results of the m‐sub provide real‐world insight into the outcomes of CRT, and will be useful for future evaluations of ICI maintenance therapy after CRT.

Prognostic Impact of Pneumonitis After Durvalumab Therapy in Patients With Locally Advanced Non-small Cell Lung Cancer

“…The incidence of pneumonitis in this study was similar to that in the Japanese subgroup of the PACIFIC study [2] as well as that in a retrospective Japanese study of chemoradiotherapy for unresectable Stage III NSCLC [3]. Horinouchi et al reported that CRT-related pneumonitis occurred about 10-12 weeks after the completion of CRT in patients with NSCLC [3], consistent with the time of onset of pneumonitis in the present study. Pneumonitis induced with ICI, including durvalumab, occurred at a rate of 1.0% in a phase I/II trial [8].…”

“…We demonstrated that Grade 2 pneumonitis after durvalumab administration following CRT was not associated with a poor prognosis, while pneumonitis before durvalumab administration following CRT was associated with a poor PFS. In our study, the PFS was compatible with that observed in the Japanese subgroup of the PACIFIC trial [3], con rming the reliability of our study.…”

“…In the PACIFIC trial, the incidence of any-grade pneumonitis was 33.9% in all patients and 73.6% in the Japanese subgroup [2]. Horinouchi et al reported an incidence of radiation pneumonitis after CRT of 72.9% among Japanese patients with Stage III NSCLC in a retrospective cohort study that was performed before durvalumab approval [3]. and this incidence was similar to the incidence of pneumonitis in the Japanese subgroup of the PACIFIC study [3].…”

“…Horinouchi et al reported an incidence of radiation pneumonitis after CRT of 72.9% among Japanese patients with Stage III NSCLC in a retrospective cohort study that was performed before durvalumab approval [3]. and this incidence was similar to the incidence of pneumonitis in the Japanese subgroup of the PACIFIC study [3]. Haratani et al reported that the development of immune-related adverse events (irAE) was associated with improved overall survival (OS) and progression-free survival (PFS) in patients with advanced or recurrent NSCLC [4].…”

TMEM229A suppresses non‑small cell lung cancer progression via inactivating the ERK pathway

“…Moreover, lung cancer is typically classified as small-cell lung cancer (SCLC) and non-SCLC (NSCLC) ( 2 ), with NSCLC being the major type of lung cancer and accounting for 85% of all cases ( 2 ). Despite significant improvements in NSCLC treatment, including surgery ( 4 ), chemotherapy ( 5 , 6 ), radiotherapy ( 7 ), targeted therapy ( 8 – 10 ) and immunotherapy ( 11 ), the 5-year survival rate of patients with NSCLC is only 15% ( 2 , 12 ). This is due to the absence of early sensitivity and specificity diagnostic biomarkers ( 13 ), drug resistance ( 14 ) and distant metastasis ( 15 ).…”