Pretreatment levels of serum alkaline phosphatase are associated with the prognosis of patients with non‑small cell lung cancer receiving immune checkpoint inhibitors

Abstract

Immune checkpoint inhibitors (ICIs) have been an encouraging treatment method in non-small cell lung cancer (NSCLC). However, bone and liver metastases are considered to restrain immunotherapy efficacy. Since serum alkaline phosphatase (ALP) is associated with bone and liver metastases, it was investigated whether serum ALP could be a novel biomarker to predict the efficacy of ICIs treatment. In the present study, 143 patients with NSCLC receiving ICIs treatment were retrospectively analyzed. The objective response rate (ORR) was compared between the ALP high and low groups, bone metastasis and non-bone metastasis groups, and liver metastasis or non-liver metastasis groups. The associations between clinical characteristics, including ALP level, bone or liver metastasis and median progression-free survival (mPFS) time were analyzed by univariate and multivariate Cox regression analysis. It was found that bone metastasis was associated with a lower ORR (24 vs. 43%; P<0.05) and shorter mPFS (10.2 vs. 17.3 months; P=0.010) in patients with NSCLC receiving ICIs. Liver metastasis was associated with lower ORR (22 vs. 38%; P<0.05), but not with mPFS (P=0.119). The ALP level was higher in patients with bone or liver metastasis than in those without (119.6 or 103.6 vs. 83.3 U/l, respectively; P<0.05). Higher ALP levels were also associated with bone or liver metastasis, lower ORR (20 vs. 39%; P<0.05) and shorter mPFS (8.5 vs. 15.4 months; P=0.009). Cox regression analysis demonstrated that ALP was an independent prognostic indicator of mPFS (hazard ratio, 1.856; 95% confidence interval, 1.030-3.343; P=0.040). In conclusion, pretreatment levels of serum ALP might be a predictive indicator of clinical outcome in patients with NSCLC after ICIs treatment.

Can blood-based markers predict RECIST progression in non-small cell lung cancer treated with immunotherapy?

“…While research on ALP has demonstrated their potential as biomarkers across different tumour types, its role in NSCLC remains uncertain (Jiang et al 2023 ), and literature concerning NSCLC patients receiving immunotherapy is limited. Yang et al ( 2023 ) found that higher levels of pre-treatment ALP are associated with lower overall response rate, and shorter median progression-free survival (mPFS) in patients with NSCLC treated with immune checkpoint inhibitors and that ALP is an independent prognostic indicator of mPFS. Julian et al ( 2022 ) found that high levels of ALP were a risk increasing prognostic factor in advanced NSCLC patients receiving anti-PD-1/PD-L1 immune checkpoint inhibitors.…”

Do alkaline phosphatases have great potential in the diagnosis, prognosis, and treatment of tumors?

“…On the other hand, it is worth noting that a deficiency in ALP can also have negative implications for cancer patients. Studies have shown that low levels of ALPs are linked to poorer outcomes in individuals with specific types of tumors, such as CRC, breast cancer, and NSCLC ( 44 , 47 - 52 , 54 , 55 ). This is because reduced ALP activity may be indicative of decreased differentiation among cancer cells, meaning they are less specialized and more likely to grow uncontrollably.…”

“…ALP has also been studied as a potential biomarker in NSCLC patients, though the results of studies have been inconsistent ( 38 ). Some studies have reported that high levels of ALP are associated with a poorer prognosis and shorter survival time in NSCLC patients, while others have found no significant correlation between ALP levels and prognosis in NSCLC ( 38 , 54 , 55 ). In addition to being a potential marker of bone metastases, ALP may also be involved in promoting tumor growth and invasion in NSCLC.…”