PD-L1 Inhibitor Rechallenge After Immunotherapy-Related Pneumonitis in Patients With Lung Cancer

Checkpoint inhibitor pneumonitis is an important immune-related adverse event associated with immune checkpoint inhibitor treatment. Some patients with lung cancer may require immune checkpoint inhibitor rechallenge after recovery from pneumonitis because of tumor progression or limited subsequent treatment options. However, evidence regarding the safety and effectiveness of PD-L1 inhibitor rechallenge after checkpoint inhibitor pneumonitis remains limited.

This is a multicenter, ambispective, observational cohort study. The time perspective is classified as Other because the study combines retrospective review of existing medical records with prospective follow-up according to routine clinical visits.

Adults with histologically confirmed lung cancer who developed checkpoint inhibitor pneumonitis will be included. Participants will be classified into three cohorts according to routine clinical treatment decisions:

1. PD-L1 inhibitor rechallenge cohort;
2. PD-1 inhibitor rechallenge cohort; and
3. No immune checkpoint inhibitor rechallenge cohort.

No participant will be randomly assigned to treatment, and the study protocol will not require any specific treatment, additional visit, laboratory test, or imaging examination. Treatment decisions will be made independently by the treating physicians.

Clinical information will be obtained from routine medical records and follow-up assessments. Data collected will include demographic characteristics, lung cancer characteristics, previous cancer treatment, initial checkpoint inhibitor treatment, characteristics and management of checkpoint inhibitor pneumonitis, subsequent antitumor treatment, immune-related adverse events, tumor response, disease progression, and survival.

The primary objective is to compare the recurrence of checkpoint inhibitor pneumonitis after PD-L1 inhibitor and PD-1 inhibitor rechallenge. Secondary objectives include comparisons of progression-free survival, overall survival, recurrence or new onset of other immune-related adverse events, objective response rate, and disease control rate. Exploratory analyses will evaluate clinical factors associated with the safety and effectiveness of PD-L1 inhibitor rechallenge.

A non-probability sampling approach will be used to include eligible cases available at the participating centers. The planned enrollment is 150 participants, with approximately 50 participants in each cohort.