Efficacy of immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma and predictive potential of mutated TP53

Abstract

Objective

Pulmonary sarcomatoid carcinoma (PSC) is a rare, heterogeneous subgroup of non-small cell lung cancer (NSCLC). Patients with advanced PSCs have poor survival due to resistance to chemotherapy and radiotherapy, and narrow access to targeted therapy. Immune checkpoint inhibitors (ICIs) offer new hope, whereas data on their effectiveness is limited.

Methods

This retrospective study collected medical records of patients with advanced PSCs from January 2010 to March 2024 across two centers in China, analyzing demographic, treatment, and survival data. Sixty cases were included.

Results

In tumors tested for PD-L1 expression, 80 % had PD-L1 positivity, and 60 % exhibited TPS ≥ 50 %. The most frequently mutated genes in PSCs were TP53 (25.9 %), KRAS (22.8 %), MET (7.4 %), BRAF (7.4 %), CDKN2A/B (7.4 % each), and EGFR (6.2 %). Median OS of patients with advanced PSCs receiving anti-PD-1 or anti-PD-L1 antibodies in any line was significantly longer compared to those who did not (NR vs. 11.2 months, p = 0.015). ICI application was an independent favorable factor for the prognosis of patients diagnosed with advanced PSC (HR 0.32, p = 0.008). In the subgroup treated with ICI-based therapies, ORR and DCR were 34.5 % and 82.8 %, respectively. The mPFS and mOS of ICI-based therapies were 12.5 and 16.0 months, respectively. TP53 mutations and PD-L1 TPS ≥ 80 % were associated with prolonged PFS (p = 0.021, p = 0.035) and OS (p = 0.013 and p = 0.018).

Conclusions

Positive or high PD-L1 expression was prevalent in advanced PSCs. Anti-PD-1 or anti-PD-L1 antibodies were associated with favorable prognosis, and should be considered a key treatment option for patients with advanced PSC lacking actionable driver mutations. In addition to PD-L1 expression, TP53 mutations have the potential to predict the efficacy of ICIs in treating patients with advanced PSC and its prognostic significance deserves further validation in larger prospective studies.