ONCAlert | Upfront Therapy for mRCC

Targeted Therapy for Advanced Squamous Cell Lung Cancer

Charu Aggarwal, MD, MPH, Corey J Langer, MD, Mary W. Redman, MD, et al
Published Online: Jul 08,2016

Squamous cell cancer offers distinct therapeutic challenges by virtue of presentation in older patients, its physical location in the chest, pattern of metastasis and association with comorbidities that can compromise treatment delivery and exacerbate toxicity.

Abstract


Squamous cell lung cancer is a unique subset of non-small cell lung cancer (NSCLC), with an aggressive phenotype. Unlike adenocarcinoma of the lung, where genomic profiling is part of the standard of care, and targeted therapies are routinely used, there are limited data on the activity and efficacy of targeted agents for this subset of patients. Squamous cell cancer also offers distinct therapeutic challenges by virtue of presentation in older patients, its physical location in the chest, pattern of metastasis and association with comorbidities that can compromise treatment delivery and exacerbate toxicity. Over the last decade, we have made tremendous progress in our understanding of the biology and molecular characteristics of this disease. Novel targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab have yielded improvements in survival that are also seen in squamous cell NSCLC. Additionally, with the availability of genomic sequencing, we are now able to offer precise targeting for relevant actionable targets. Herein, we review the currently available and approved therapeutic agents for the management of metastatic squamous cell NSCLC and clinical trials focusing on targeted therapy.
 

Introduction


Lung cancer remains the most common cause of cancer related mortality in the United States.1 Of all lung cancer cases, over 85% are classified as non-small cell lung cancer (NSCLC), with squamous cell carcinoma (SqCC) comprising approximately 30%. SqCC, once the most common subtype of NSCLC, has declined in incidence over the past 2 decades, mainly related to an overall decline in the incidence of smoking patterns and changes in cigarette filters, which facilitate distal delivery of tobacco smoke in the lungs.2 The latter has contributed to an increase in incidence of adenocarcinoma, which accounts for the majority of the patients with NSCLC.3 Despite the declining incidence, lung SqCC remains a common malignancy, accounting for approximately 85,000 new cases in the USA each year and over 400,000 worldwide. SqCC poses many therapeutic challenges related to patient demographics, tumor characteristics and tumor biology. Patients tend to be older, with a high incidence of smoking, and a higher incidence of comorbidities, including low pulmonary reserve and presence of COPD.3,4 Additionally, SqCC often involves the central airways, and the location of these tumors in proximity to large blood vessels can present treatment challenges, including bleeding and hemoptysis, which, in turn, can contraindicate the use of certain therapeutic agents.4

With the availability of widespread genomic sequencing, and the introduction of specific targeted agents for subsets of patients with adenocarcinoma, such as those with activating mutations in the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene rearrangements, survival for patients with non-squamous metastatic NSCLC has significantly improved. 5-7 At the same time, therapeutic progress in squamous cell lung cancer has been relatively slow, with relative stagnation of survival numbers, in the 9–11 month range, without substantial improvement up until very recently.8 With the exception of the newly approved necitumumab, there have been no other US Food and Drug Administration (FDA) approvals specifically for SqCC of the lung. Treatment for SqCC of the lung remains an unmet need, and novel treatment strategies are needed, including specific targeted therapies, which would provide clinically meaningful outcomes without adversely affecting quality of life.

Recently, molecular genotyping has led to the application of targeted agents for mutations prevalent in SqCC.9 This overview of the targeted treatments of squamous cell lung carcinoma highlights these recent molecular advances and discusses the potential role of newer molecular agents currently being evaluated for the treatment of advanced SqCC.



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Targeted Therapy for Advanced Squamous Cell Lung Cancer
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