In this review, we summarize the efficacy of PD-1/PD-L1 monoclonal antibiodies in patients with EGFR-mutant lung cancer patients; provide evidence to analyze the potential reason why these patients cannot benefit from anti-PD-1/PD-L1 treatment, and explore the strategy that shoud be adopted in the future.
Immunotherapy based on programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors may result in new treatment directions and a paradigm shift for Chinese patients with lung cancer.
In combination with anti-PD-1 inhibitors, pegilodecakin increased the responses in RCC and lung cancer with efficacy agnostic to PD-L1 status and tumor mutational burden.
Indeed, PD1 and PD-L1 were expressed at a higher level in lung cancer cell lines, tumor tissues, and importantly, in SCLC cells resistant to cisplatin (H69R, H82R), when compared to respective controls.
Additionally, in a multivariable analysis, PD-L1 positivity was independently associated with lower lung cancer-specific (multivariable HR = 0.24; 95% CI = 0.058-0.67; P = 0.0039) and overall (multivariable HR = 0.29; 95% CI = 0.11-0.61; P = 0.0006) mortality.
Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer.
This approval expands the pembrolizumab indication in second-line treatment of lung cancer to include all patients with programmed death-ligand 1-expressing non-small cell lung cancer.
Treatment with selective anti-PD1, anti-PD-L1 and/or anti-CTLA-4 monoclonal antibodies (mAbs) has been a revolution in the therapeutic scenario of several cancer types, with the highest clinical efficacy in melanoma and in lung cancer.
In a Cox model adjusting for stage, high PD-L1(+) cell burden remained a significant predictor of mortality (HR = 3.85; 95% confidence interval, 1.64-9.09; <i>P</i> = 0.002).<b>Conclusions:</b> PD-L1 expression is detectable in two distinct cell populations in the peripheral blood of lung cancer patients and is associated with worse survival.<b>Impact:</b> These findings could represent a step forward in the development of minimally invasive liquid biopsies for the profiling of tumors.
These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer.
Neutralizing antibodies targeting immune checkpoint programmed cell death protein 1 (PD-1) or its ligand (PD-L1) have been particularly successful for tumor types with limited therapeutic options such as melanoma and lung cancer.
In total, 26 eligible primary studies were identified, all of which reported on the test validation metrics associated with PD-L1 IHC tests in lung cancer, most using immunohistochemistry testing.
Median OS of EGFR-mutated or ALK-rearranged lung cancer was 78.6 months in PD-L1 positive group and 93.4 months in PD-L1 negative group (HR 0.47, 95%CI 0.23-0.76, P = 0.005).
Targeting immune checkpoint pathways, such as programmed death ligand-1 (PD-L1, also known as CD274 or B7-H1) or its receptor programmed cell death-1 (PD-1) has shown improved survival for patients with numerous types of cancers, not limited to lung cancer, melanoma, renal cell carcinoma, and Hodgkin lymphoma.