PD-(L)1 agents have revolutionized the treatment paradigms of non-small cell lung cancer (NSCLC). In addition to PD-L1 score, predictive biomarkers for PD-(L)1 therapies are limited. Us and others have previously shown that systemic inflammation, indicated by elevated C-reactive protein (CRP) level, is associated with a poor prognosis in PD-(L)1 treated.
We collected all NSCLC patients (n=314) who had undergone tumor PD-L1 tumor proportion score (TPS) analysis at Oulu University Hospital between 2015-21. CRP levels, treatment history, immune checkpoint inhibitor (ICI) therapy details, and survival were collected from electronic patient records. The patients were divided into two categories based on plasma CRP levels (≤10 vs >10) and PD-L1 TPS (<50 vs ≥50).
In the whole cohort (n=314), CRP level of ≤10mg/l was associated with improved overall survival in univariate (HR 0.30, Cl 95% 0.22-0.41) and multivariate analyzes (HR 0.42, CI 95% 0.28-0.66). Among the ICI treated (n=55), both CRP of ≤10 and PD-L1 TPS of ≥50 were associated with improved progression-free survival (PFS) in univariate (HR 0.45, CI 95% 0.23-0.89; HR 0.49, CI 95% 0.25-0.94) and multivariate (HR 0.44, CI 95% 0.22-0.86; HR 0.46, CI 95% 0.24-0.92) analyzes. The combination of high PD-L1 TPS (≥50) and CRP (>10) carried a high negative predictive value among the ICI treated with a median PFS of 3.22 months (CI 95% 0.67-5.77) which was very similar to patients with low PD-L1 (3.35 months, CI 95% 1.33-5.37). Univariate and multivariate analysis for PFS (IO) and OS (IO).
Univariate Multivariate HR CI (95%) HR CI (95%) PFS (IO) CRP ≤10 vs. >10 0.449 0.227-0.886 0.435 0.220-0.862 PD-L1 ≥50 vs. <50 0.485 0.250-0.942 0.464 0.235-0.917 OS (IO) CRP ≤10 vs. >10 0.479 0.225-1.021 0.536 0.248-1.159 PD-L1 ≥50 vs. <50 0.385 0.180-0.825 0.387 0.175-0.875
Adding plasma CRP levels to PD-L1 TPS significantly increased the predictive value of sole PD-L1 and patients with high CRP bared little benefit from PD-(L)1 therapies regardless of PD-L1 score. The study highlights combined evaluation of plasma CRP and PD-L1 TPS as negative predictive marker for ICI therapies.
The authors.
Finnish Cancer Institute.
S.M.E. Iivanainen: Financial Interests, Personal, Invited Speaker: Roche, MSD, Boehringer Ingelheim, Takeda, BMS, Novartis, Pierre-Fabre, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca; Financial Interests, Personal, Research Grant: Boehringer Ingelheim. J.P. Koivunen: Financial Interests, Personal, Advisory Board: Merck Sharp Dome, BMS, AstraZeneca, Pfizer, Roche, Boehringer Ingelheim, Takeda, Amgen; Financial Interests, Personal, Full or part-time Employment: Faron Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Faron Pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, Roche. All other authors have declared no conflicts of interest.