Investigational therapies for squamous cell lung cancer: from animal studies to phase II trials

ABSTRACT

Introduction: It remains challenging to treat squamous cell lung cancer (SCC) with limited therapeutic options. However, recent breakthroughs in targeted therapies and immunotherapies have shed some light on the management of this deadly disease.

Areas covered: The article first reviews the current treatment options for advanced SCC, especially recent FDA approved molecular agents (afatinib, ramucirumab and necitumumab) and immunotherapies (nivolumab, pembrolizumab and atezolimumab). We then provide an overview on investigational therapies with data ranging from preclinical to phase II studies, focusing on new cytotoxic agents, emerging molecularly targeted agents (including a PARP inhibitor for Homologous Recombinant Deficiency positive SCC) and novel immunotherapeutic strategies.

Expert opinion summary: Identification of potential therapeutic targets, development of novel clinical trials and the rapid approvals of immune checkpoint inhibitors have shifted the management paradigm for squamous cell lung cancer. On the other hand, continued efforts are needed to identify the predictive biomarkers and to investigate novel mechanistically-driven mono- and combination therapies. We need to learn more about the biology behind immune checkpoint blockade and tumor genomics in SCC for better patient selection and future trial design.

KEYWORDS:

• Squamous cell lung cancer
• immunotherapy
• targeted therapy
• novel therapy

Article highlights

• Squamous cell lung cancer is a challenging subset of NSCLC to treat, at least partly due to the rare incidence of targetable driver mutations.

• Recently approved molecular agents (afatinib, ramucirumab and necitumumab) and immunotherapies (nivolumab, pembrolizumab and atezolimumab), especially the latter, have shifted the treatment landscape for squamous cell lung cancer although the clinical benefits remain relatively modest.

• Development of novel chemotherapy and molecularly-targeted agents remains important in this exciting era of immunotherapy. Additionally, further studies to identify the optimal immunotherapeutic strategies (monotherapy versus combination) in different disease settings are needed.

• Continued efforts are needed to identify predictive biomarkers for better patient selection.

• Clinical trial participation for patients with metastatic SCC is an important therapeutic option that should be encouraged whenever possible.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.