For which lung cancer patients is re-administration of immune checkpoint inhibitors effective?

Objective: Currently, immune checkpoint inhibitors (ICIs) play a central role in the treatment of lung cancer. However, ICI re-administration is still uncommon, and its utility should be evaluated as early as possible. Patients and Methods: Twenty-five patients who received ICIs twice or more in any of the drug treatment lines for advanced/relapsed non-small cell lung cancer were included. OS, PFS, ORR, and DCR were examined, and factors such as age, sex, histopathological type, PD-L1 expression, whether radical surgery was performed, driver gene mutations, and immune-related adverse events (irAEs), were evaluated for their relevance and as prognostic factors. Results: Of the 25 patients, 17 were men and 8 were women, with an average age of 68 ± 8.4 (range, 48-85 years), and histology was non-squamous cell carcinoma/squamous cell carcinoma in 19/6 cases. One driver gene mutation positive case was included. PD-L1 TPS was ≥50%/1-49%/0-1%/ unknown in 7/8/5/5 cases. The first ICI administered was pembrolizumab/nivolumab/atezolizumab in 5/13/7 cases. The median number of courses was 9 (range, 1-52) months, and the median PFS was 9 (95% CI, 6.0-12.0) months. Cytotoxic chemotherapy or radiation therapy was administered to 6 patients during the interval up to re-administration. The second ICI administered was pembrolizumab/nivolumab/atezolizumab in 5/8/12 cases, and all patients received antibody drugs different from those given as the first ICI. The median number of courses was 5 (range, 1-24), and the median PFS was 3 months (95% CI, 1.0-5.0) months. In 5 of the 6 patients (24%) who achieved PFS of 6 months or longer after re-administration, the order of administration was anti-PD-1 antibody to anti-PD-L1 antibody. Conclusion: The effect of re-administration is limited, but it may be effective depending on the type of cases and the order of ICI administration. Further studies are required to verify its effectiveness.