Pneumonitis history linked to ICI/chemo-related pneumonitis in NSCLC patients

Patients with advanced non-small-cell lung cancer (NSCLC) who have a past medical history of pneumonitis are at increased risk of treatment-related pneumonitis (TAP) from immune checkpoint inhibitor (ICI) regimens or chemotherapy alone, an analysis of clinical trial and real-world data has shown.

According to the investigators, data from the study’s real-world cohort suggest that radiotherapy (RT) is a frequent cause of pneumonitis. “Only in clinical trial data, and only for patients without a past medical history of pneumonitis, was there a demonstrated difference in the incidence of TAP between the ICI and chemotherapy groups,” they pointed out. [Liu Q, et al, AACR 2020 Virtual Annual Meeting I, abstract CT086]

In the study, investigators from the US FDA, Syapse (a medical data company headquartered in San Francisco, California, US), and Advocate Aurora Health in Milwaukee, Wisconsin, US, evaluated TAP in patients with advanced NSCLC based on pooled data from eight randomized trials (n=6,491) comparing ICI (+/- chemotherapy) with chemotherapy, as well as real-world data of patients (n=1,262) treated with ICI (+/- chemotherapy) or chemotherapy without concurrent RT.

“We found a higher incidence of TAP among ICI-treated patients compared with those receiving chemotherapy alone. While directionally aligned, the clinical trial data set showed a stronger signal than the real-world data sample,” reported investigator Dr Qi Liu of the Office of Clinical Pharmacology, US FDA.

In the clinical trial data set, the incidence of TAP was 4.5 percent for patients in the ICI arms (n=3,723), compared with 1.0 percent for those in the chemotherapy arms (n=2,768). In the real-world cohort, the incidence of TAP was 3.3 percent among patients treated with ICIs (n=615), compared with 2.3 percent among those treated with chemotherapy (n=647).
There was also an increase in TAP in patients with a past medical history of pneumonitis, regardless of treatment arm, in both the clinical trial and real-world cohorts.

In clinical trials, the incidence of TAP in the ICI arms was 16.7 percent among 30 patients with a past medical history of pneumonitis, compared with 4.4 percent among 3,693 patients with no such history. The incidence of TAP in the chemotherapy-alone arms was 11.1 percent and 1.0 percent, respectively, among 18 and 2,750 patients.

In the real-world cohort, the incidence of TAP in ICI-treated patients was 14.3 percent among 21 patients with a past medical history of pneumonitis, compared with 2.9 percent among 594 patients no such history. The incidence of TAP in patients treated with chemotherapy alone was 8.3 percent and 2.2 percent among 12 and 635 patients, respectively.

“Most patients with a past medical history of pneumonitis or TAP in the real-world data set had received prior RT,” said Liu.

“Pneumonitis at any time in the real-world cohort was strongly associated with RT in both the ICI and chemotherapy groups, with 73 percent of all diagnoses of pneumonitis due to RT,” the investigators pointed out.

Limitations of the study included the small number of patients with past medical history of pneumonitis, the relatively small numbers of TAP cases in the real-world cohort, and the variable follow-up duration.

“The next steps will be to further explore past chest RT and infectious pneumonitis as predictors of ICI-induced pneumonitis, as well as the incidence of pneumonitis in different treatment populations, including ICI alone vs ICI plus chemotherapy, ICI plus tyrosine kinase inhibitors [TKIs], and TKIs alone,” said Liu.