Response to cancer immunotherapy for p53 antibody-positive non-small cell lung cancer according to treatment regimen.

Abstract

8589 Background: Cancer immunotherapy has enabled long-term survival in advanced non-small cell lung cancer (NSCLC), but there are some patients with resistance to cancer immunotherapy. Mutations in the p53 gene have been reported to suppress immunity in the tumor immune microenvironment and influence resistance to cancer immunotherapy. Serum p53 antibody is an autoantibody produced in association with p53 gene mutations. However, it is unclear whether p53 antibody-positive NSCLC correlates with treatment response to cancer immunotherapy, particularly whether treatment response differs according to the treatment regimen. Methods: Participants were patients with advanced NSCLC who received immune checkpoint inhibitors (ICI) with or without chemotherapy at our hospital from November 2018 to June 2024. Blood samples were obtained before and after treatment with ICI and serum p53 antibody levels were measured. We compared the serum anti-p53 antibody and treatment response (early progressive disease, progression-free survival, and overall survival). Furthermore, we investigated whether treatment response of cancer immunotherapy in p53 antibody-positive NSCLC differs according to the treatment regimen. Results: A total of 173 patients were enrolled (mean age 69.4 years, 76.7% male, 58.4% adenocarcinoma). The regimen of ICI with chemotherapy was more common in 130 cases (75.1%) than ICI alone. There were 70 patients (40.4%) who were positive for serum p53 antibody before treatment. The p53-positive group had a significantly higher early progressive disease than the p53-negative group in the patients who received ICI with chemotherapy (28.6% vs 15.5%, p = 0.04). Multivariate analysis showed that serum p53 antibody was the only factor significantly associated with early progressive disease (HR 3.11, 95%CI 1.19-8.50, p = 0.02). PFS was significantly shorter in the p53-positive group than in the p53-negative group in patients with PD-L1 low expression (0-49%) (3.7m vs 7.2m, p = 0.01). Regarding the impact of treatment regimens on treatment response, there was no difference based on ICIs with or without chemotherapy. However, the group that combined anti-VEGF antibodies with ICIs had a significantly lower early progressive disease rate than the group that did not combine them (14.3% vs 30.2%, p = 0.03). Conclusions: Serum p53 antibody influenced the therapeutic efficacy of cancer immunotherapy in NSCLC. p53 antibody-positive NSCLC demonstrated differing treatment responses depending on therapeutic regimen. We believe that the combination of ICIs and anti-VEGF antibodies is a promising treatment option for p53 mutation-positive NSCLC.