Exploring the potential of immuno-oncology-based treatment for patients with non-small cell lung cancer

Abstract

Immune evasion is recognized as a key strategy for cancer survival and progression. With increased understanding of immune escape mechanisms, the development of immunotherapies to restore anti-tumor immune responses has flourished. Immuno-oncology (I-O) agents targeting checkpoints in the immune regulation cascade currently form the mainstay of approaches of cancer immunotherapy. Since initial success in melanoma, evidence for the notable effects of the I-O modality has been expanding, with numerous clinical studies underway or completed in a variety of solid tumors, including non-small cell lung cancer. This review highlights the rationale and potential role of immunotherapy in non-small cell lung cancer management, with a focus on immune checkpoint inhibitors. We also discuss the potential for I-O-based combination therapy.

Keywords:

• cytotoxic T-lymphocyte-associated antigen 4
• immune checkpoint inhibitors
• immunotherapy
• ipilimumab
• lung cancer
• nivolumab
• non-small-cell lung cancer
• programmed cell death protein 1

Financial & competing interests disclosure

The authors take full responsibility for the content of this publication, and confirm that it reflects their viewpoint and medical expertise. D Heigener has received lecture fees from Bristol-Myers Squibb, Boehringer Ingelheim, Roche and Lilly, and acted as an advisor for Boehringer Ingelheim and Roche. M Reck has received lecture fees from and acted as an advisor for Bristol-Myers Squibb, Boehringer Ingelheim, Roche and Lilly. StemScientific, funded by Bristol-Myers Squibb, provided writing and editing support. Bristol-Myers Squibb did not influence the content of the manuscript, nor did the authors receive financial compensation for authoring the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Immune evasion is now recognized as a hallmark of tumor progression and malignancy.

• Immuno-oncology (I-O) aims to restore immune-mediated destruction of the tumor.

• The most promising strategy lies with immune regulation using checkpoint inhibitors.

• These agents target specific inhibitory/co-stimulatory molecules such as cytotoxic T-lymphocyte-associated antigen 4 (e.g., ipilimumab) and programmed cell death protein 1 (e.g., nivolumab) with the effect of disinhibiting and thus, promoting, the activation of tumor-specific cytotoxic T lymphocytes.

• Clinical trials of immune checkpoint blockade have reported striking and durable clinical outcomes in a variety of tumors, including non-small-cell lung cancer.

• In addition to their significant anticancer effects, these immunotherapy agents also have a favorable toxicity profile, with more manageable adverse effects than current therapies.

• However, as these adverse effects are unique, steps to raise awareness, educate clinicians and putting in place standardized management pathways are necessary.

• Immune checkpoint agents have considerable potential not only as single agents, but also as part of combination therapy with other immunotherapies, or current standard therapies (including chemotherapy, radiotherapy and targeted therapy).

• A number of Phase III clinical trials in NSCLC are currently ongoing to evaluate these agents and their results are eagerly anticipated, in the hope that they will transform present therapeutic regimes in this lethal disease.

Notes