Anti PD-1 and PDL-1 Immunotherapy in the Treatment of Advanced Non- Small Cell Lung Cancer (NSCLC): A Review on Toxicity Profile and its Management

Abstract

The better understanding of immunology and antitumor immune responses have prompted the development of novel immunotherapy agents like PD-1 checkpoint inhibitors (anti-PD-1 and anti- PDL-1 antibodies) that improve the capacity of the immune system to acknowledge and delete tumors, including lung cancer. Currently, two anti-PD-1 (nivolumab and pembrolizumab) and one anti- PD-L1 (MPDL-3280A) agents are in advanced stages of development in advanced or metastatic non-small cell lung cancer (NSCLC). Among these, nivolumab demonstrated a survival benefit versus docetaxel in refractory squamous NSCLC, reporting 41% reduction in risk of death (median overall survival: 9.2 versus 6.0 months; objective response rate: 20% versus 9%), and better safety profile than standard-of-care chemotherapy (grade 3-4 adverse events: 7% versus 55%). However, the enhancement of immune response to cancer targeting specific immune regulatory checkpoints is associated with a toxicity profile different from that related to traditional chemotherapeutic agents and molecularly targeted therapies. The success of immunotherapy is related to ongoing evaluation/identification and treatment of these immunerelated side effects. Herein, first clinical results of PD-1 agents in lung cancer are reviewed, focusing on toxicity profile and its management.

Tumor-targeted Nanoparticle Delivery of HuR siRNA Inhibits Lung Tumor Growth In Vitro and In Vivo By Disrupting the Oncogenic Activity of the RNA-binding Protein HuR

“…Further, recent reports on the role of PDL1-PD1 in suppressing host immune T-cells begs the question if HuR-TfNP treatment will impact the PDL1-PD1 signaling and alter the host immune system to enhance the anti-tumor immune activity. These questions while of interest are beyond of the scope of the present study but warrant investigation in the future [63, 64]. In conclusion, we have demonstrated HuR-TfNP treatment effectively inhibits lung cancer growth both in vitro and in vivo .…”

Entinostat Neutralizes Myeloid-Derived Suppressor Cells and Enhances the Antitumor Effect of PD-1 Inhibition in Murine Models of Lung and Renal Cell Carcinoma

“…Clinically, anti-PD-1 immunotherapy has shown prolonged stabilization of disease in approximately 40% of patients with RCC and lung cancer (1,2,15) leading to improvements in overall survival in these indications. Following the previous study in the RENCA model demonstrating tumor growth inhibition, we examined the survival outcome for the entinostat and anti-PD-1 antibody combination.…”

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

“…181 Immune-related AEs, such as pneumonitis, may occur with immune checkpoint inhibitors. 173,178,[182][183][184][185][186][187][188][189] Intravenous high-dose corticosteroids should be administered based on the severity of the reaction for patients with immune-mediated AEs. Immune checkpoint inhibitors should be discontinued for patients with severe or life-threatening pneumonitis and should be withheld or discontinued for other severe or life-threatening immune-mediated AEs when indicated (see prescribing information).…”