Expanding TKI Therapy in Advanced Lung Cancer

Anita T. Shaffer
Published Online: Wednesday, October 9, 2013
Dr. Paul Bunn

Paul A. Bunn Jr, MD

Amid rapid progress in the treatment of advanced lung cancer, several leading organizations have joined in developing new guidelines for the optimal use of molecular testing to help select patients for therapy with tyrosine kinase inhibitors (TKIs).1

And one of the key messages to emerge from the guidelines is that even patients with stage 4 disease and poor performance status (PS) scores should be considered as candidates for TKI therapy, according to Paul A. Bunn Jr, MD, a professor of Lung Cancer Research at the University of Colorado School of Medicine in Denver (Table 1).

Bunn discussed the role of TKIs as part of his “Current Status of Advanced Lung Cancer” presentation, which he delivered at the 14th International Lung Cancer Congress. Physicians’ Education Resource (PER) hosted the congress, held July 25-27 in Huntington Beach, California.

Bunn, a founding director of the University of Colorado Cancer Center, is also the executive director of the International Association for the Study of Lung Cancer (IASLC), which developed the guidelines in collaboration with the College of American Pathologists and the Association for Molecular Pathology.

Clinical decisions about treating patients with lung cancer formerly were made based on clinical features, particularly PS scores, Bunn noted. Now, molecular advances have resulted in FDA-approved TKIs for patients with epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene translocations, and more agents are in development.

Yet, Bunn said that nearly one-third of patients with lung cancer never receive any treatment, according to Surveillance, Epidemiology and End Results data. He noted that 60% of patients with lung cancer, regardless of histology, have metastatic disease.

Table 1. Treatment Algorithm for Advanced Lung Cancer

Treatment Algorithm for Advanced Lung Cancer

CR indicates complete response; EGFR, epidermal growth factor receptor; PR, partial response, PS, performance score; SD, stable disease.
Adapted from Bunn PA. Current status of advanced lung cancer. Presented at:14th International Lung Cancer Congress; July 25-27, 2013; Huntington Beach, CA. Reprinted with permission.

“Those patients frequently never even get to medical oncologists,” he said. “Certainly, patients with PS3 and arguably PS4 [scores] are eligible to receive oral tyrosine kinase inhibitors if they have a driver abnormality. It’s important for those of us in thoracic oncology to let our primary care physicians know that lung cancer doesn’t mean hospice."

In an interview, Bunn said that the new joint guidelines recommend that “every patient with stage 4 lung cancer that has any adenocarcinoma component or is too small to characterize—or has clinical features suggesting one of these driver abnormalities—that tumor should be tested.” The guidelines recommend EGFR and ALK testing.

He said many patients “are sent to hospice without any treatment and also without any molecular testing. Now these TKIs are oral, don’t require IV, and they don’t have grade 3 and 4 life-threatening toxicities, so patients who are PS3, some patients who are on ICUs, can benefit from these.

“Even sick patients who have lung cancer should have this molecular testing,” Bunn added. “They may be too sick for chemotherapy, but they’re not too sick for these oral tyrosine kinase inhibitors.”

Importance of Histology

When it comes to histology, researchers are turning away from using the term non-small cell lung cancer (NSCLC) because it is too general to accurately describe a pathologic diagnosis or a clinical category.

The guidelines panel pointed out that a recent update of National Comprehensive Cancer Network recommendations also reflected an “evolution” in thinking about the disease. The distinction between histologic subtypes “has become critical for determining subsequent molecular characterization of tumors and patient management,” the panel said. For example, NSCLC can be classified into three different subtypes (Figure). “Non-small cell lung cancer is not an adequate term anymore,” agreed Bunn.

Bunn said that distinguishing large cell neuroendocrine from squamous and from adenocarcinoma affects whether antiangiogenic therapy or chemotherapy is employed. “Bevacizumab causes too much bleeding in squamous cancer and shouldn’t be used, and pemetrexed doesn’t work well in squamous cancer and shouldn’t be used,” he said.

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