Discussion
NSCLC, pneumonitis, tumor, cancers, thoracic irradiation, chronic lung disease
PNEUMONITIS, TUMOR, CANCERS, METASTATIC DISEASE, NSCLC, CHRONIC LUNG DISEASE
In this analysis of TAP incidence among patients with NSCLC treated with ICI or chemotherapy, we observed a higher rate of TAP diagnosis in the RCT cohort as compared with the RWD cohort. This differs from previous reports where RWD analyses reported higher incidence compared with RCT (In the RWD cohort, all patients with TAP had received thoracic radiation prior to TAP, and 55% of patients with TAP received thoracic radiation prior to index therapy. Radiation treatment status was not available for the entire general RWD cohort; however, it was available for a subset of 821 patients. In this subset of the general RWD cohort (including both patients with and without TAP), a lower proportion of patients (25%) received thoracic radiotherapy prior to index treatment compared with TAP-diagnosed patients. This suggests a potential connection between prior thoracic radiation and TAP. No substantial differences were observed between the subsets where radiotherapy status was available or not, with the exception of a higher proportion of patients with metastatic disease (at index treatment) in the subset with radiotherapy status available. Given that patients with metastatic disease are less likely to receive thoracic irradiation, especially with curative intent, use of this subset of patients as a representative sample may lead to an underestimation of the past receipt of thoracic radiotherapy in the RWD cohort. Because of questions around generalizability, potential confounding, and other differences between patient groups with or without tumor registry data, additional studies are needed to further assess the association between TAP and prior thoracic radiotherapy.The use of ICIs for the treatment of aNSCLC has increased, alongside the need for better data describing ICI-mediated pneumonitis, including the incidence, time to development, severity, and potential predisposing patient factors. Although clinical trials tend to report relatively lower pneumonitis rates among ICI-treated patients (3%–5% of patients) compared with previously reported RWD studies (Another challenge in the assessment of treatment-related pneumonitis is how to assess patients labeled or diagnosed as having radiation pneumonitis. Some studies evaluating ICI therapies have explicitly excluded patients labeled as having radiation pneumonitis from being designated as TAP (Differences in patient identification periods may also contribute to differences in observed TAP incidence between studies (whether RWD or RCT). Earlier published studies assessing patients treated prior to the approval of PD-L1 inhibitors report rates for a different distribution of ICIs compared with our more recent RWD study of patients who received one of four available ICIs as recently as September 2020. Finally, differences between earlier and more recent use of ICIs for treatment of NSCLC, including use of supportive care and patient selection for treatment may have shifted over time as physicians gain experience using ICIs with their patients with aNSCLC, resulting in lower TAP seen in this more recent study.The results of this study should be interpreted within the context of inherent limitations. To our knowledge, our study cohort is the largest U.S. real-world population studied to date; however, the sample size is still relatively small compared with the pooled RCT analysis. Because of these limitations of the data, descriptive analyses are unadjusted for potentially confounding patient characteristics such as history of chronic lung disease and line of therapy of index treatment, which does not allow any inference of causality in this study (As immunotherapies take on an increasingly prominent role in the treatment landscape for a wide range of cancers, there is an important need to better understand the incidence of and risk factors for TAP in real-world practice. In 2020, 4,720 immuno-oncology drugs were in the global development pipeline, a 22% expansion from 2019, despite the impact of the COVID pandemic (