A Phase 2 Study of Atezolizumab for Pretreated NSCLC With Idiopathic Interstitial Pneumonitis

Abstract

Introduction: Interstitial pneumonia (IP) is one of the most common and poor prognostic comorbidities in patients with NSCLC and a known risk factor for pneumonitis. Atezolizumab monotherapy is an established treatment for recurrent NSCLC and reported to have a lower risk of pneumonitis than programmed cell death protein 1 inhibitors. This study aimed to assess the safety and efficacy of atezolizumab monotherapy in patients with pretreated advanced or recurrent NSCLC with idiopathic IP. Methods: Patients with advanced or recurrent NSCLC with comorbid idiopathic, chronic fibrotic IP with % forced vital capacity of greater than 70% and no history of immune checkpoint inhibitors were enrolled. The patients received atezolizumab (1200 mg) every 3 weeks until the discontinuation criteria were met. The primary end point of this study was the 1-year survival rate. A sample size of 38 patients was set. Results: This study was terminated early owing to high incidence of pneumonitis. A total of 17 patients were enrolled, with a median age of 70 years. The median % forced vital capacity and % diffusing capacity for carbon monoxide at baseline were 85.4% and 54.4%, respectively. The incidence of pneumonitis was 29.4% (5 of 17) for all grades, 23.5% (4 of 17) for grade greater than or equal to 3, and 5.9% (1 of 17) for grade 5. A total of 57.1% patients (4 of 7) with honeycomb lung developed pneumonitis with a grade greater than or equal to 3, whereas only one patient (10%) without honeycomb lung (n ¼ 10) with grade 1 pneumonitis was found. Conclusions: Patients with NSCLC with comorbid IP as defined by the selection criteria for this study might have an increased risk of immune checkpoint inhibitor-induced pneumonitis.

Real‐world efficacy of atezolizumab in non‐small cell lung cancer: A multicenter cohort study focused on performance status and retreatment after failure of anti‐PD‐1 antibody

“…In Japanese subsets, it is generally well known that interstitial pneumonia is found in higher frequency compared with other races. Recently we reported that honeycomb lung on high resolution CT (HRCT) was a risk factor of ICI‐induced pneumonitis 12 . In the present study, three patients developed interstitial pneumonia, but honeycomb lung was not seen in these three patients.…”

Real-world evaluation of second line chemotherapy for patients with advanced non-small cell lung cancer harboring preexisting interstitial lung disease

“…Japanese phase II study evaluating atezolizumab for previously treated patients with NSCLC and ILD showed that the incidences of pneumonitis were 29.4% for all grades, 23.5% for grades ≥ 3, and 5.9% for grade 5 [35]; this indicated that patients with NSCLC and ILD have an increased risk of immune checkpoint inhibitor-induced pneumonitis. Hence, the safety of these agents in such patients is unclear, and additional safety data are warranted from a clinical trial comprising a larger and more carefully selected cohort of patients.…”

A case of pulmonary pleomorphic carcinoma with preexisting interstitial pneumonia successfully treated with pembrolizumab

“…Acute exacerbations of interstitial pneumonia were found in two patients (11%) in this phase II study, but there were no treatment‐related deaths. Another phase II study of atezolizumab for NSCLC with interstitial pneumonia was terminated early owing to 29.4% of the patients (five of 17) experiencing acute exacerbation of interstitial pneumonia 22 …”