Phase II Trial Assessing 1st Line and 2nd Line Treatment in Patients With Advanced Non-Small Cell Lung Carcinoma and Interstitial Lung Disease

Lung cancer is a leading cause of cancer-related death worldwide. Interstitial Lung Diseases are closely associated with lung cancer either as complications or comorbidities to be considered for treatment.

Recently, a survey concerning the management of lung cancer in patients with ILDs was conducted by the Interstitial Lung Diseases and Thoracic Oncology Assemblies of the European Respiratory Society. Out of 494 practitioners, mostly pulmonologists, this survey showed that the majority of metastatic patients with pulmonary fibrosis would not be treated (69%), but that 25% and 31% of clinicians would offer chemotherapy or immunotherapy, respectively.

The systemic therapy is not clearly codified. There is a risk of worsening of ILDs with most of the treatments used in lung cancer including surgery, radiation therapy or certain systemic therapies. The Japanese Society of Pneumology has recently published proposals for care. However, the Asian population is unique in its incidence of ILDs and the frequency of drug toxicities and these recommendations may not be relevant for other populations. Thus, data are still needed to validate carboplatin and weekly paclitaxel as the best regimen for first-line treatment of NSCLC patients with ILD in a caucasian population.

In 2nd line setting, immune checkpoint blocker (ICB) in monotherapy or associated with chemotherapy has become an essential part of the therapeutic arsenal in advanced NSCLC. Several agents have been shown to be superior to docetaxel, following platinum-based chemotherapy failure, and have resulted in several marketing authorizations for PD-1 inhibitors (nivolumab, pembrolizumab) and PD-L1 inhibitors (atezolizumab).

The long-term benefits of using ICBs as a second-line therapy are now clear. Survival at 5 years is 10% higher than that obtained with docetaxel alone.

The safety profile is well known in particular with a risk of pulmonary toxicity. It should be noted that in most trials, patients with ILDs were not included. Therefore, we do not have trial data from these pivotal trials in patients with concomitant ILD.

Two prospective studies are available on the use of nivolumab in the second-line setting in patients with idiopathic ILDs. The first, in an Asian population, included 6 patients. It showed an interesting response rate of 50% without grade III or IV pulmonary toxicity or worsening of at 12 weeks.

Following this, the same team proposed a multicenter phase 2 study. Included patients had mild ILDs (VCf >80%) and were treated with nivolumab in 2nd line. The primary objective was PFS at 6 months. 18 patients were treated. 3 patients developed toxicity leading to discontinuation of nivolumab including 2 patients with grade 2 pneumonitis. PFS at 6 months was 56%, response rate was 39% and disease control achieved for 72% of patients.

In a recent prospective study in Asia, atezolizumab was administered to patients with moderate IPF and advanced NSCLC. The study was stopped prematurely due to a high incidence of inflammatory pneumonitis.

Thus, data are still needed to assess the safety of ICB in NSCLC patients with ILD in second line setting.