Novel Drugs Show Promise in NSCLC

Beth Fand Incollingo @fandincollingo
Published: Monday, Jan 14, 2013
Dr Mark G. Kris

Mark G. Kris, MD

An ever-deeper understanding of the biology that drives non–small cell lung cancer (NSCLC) is sparking new treatment paradigms that include selecting targeted drugs based on patients’ biomarkers; exploiting therapies developed and approved for other forms of cancer; and investigating the value of novel agents.

In a discussion at the 2012 Chemotherapy Foundation Symposium, a panel of medical experts summarized those developments with a focus on new drugs in the pipeline for both adenocarcinoma and the significantly less common squamous cell carcinoma (SCC), for which there are currently few treatments available.

Mark G. Kris, MD, chief of the Thoracic Oncology Service at the Memorial Sloan- Kettering Cancer Center (MSKCC) in New York City, shared his excitement about the growing number of treatment options for the two-thirds of adenocarcinoma patients and 45% of SCC patients in whom driver mutations are found.

While patients with unknown driver mutations are treated with chemotherapy, he said, there are targeted treatments available for adenocarcinomas driven by EGFR or RAS mutations, or by ALK rearrangements, and researchers are investigating ways to inhibit other drivers of adenocarcinoma, as well as the mutations that drive SCC.

“The one-size-fits-all treatment of lung cancers is over,” he said. “Precise pathologic diagnosis is a must. No patient profile works, period. Test, don’t guess.”

While several of the panelists focused on treatments for adenocarcinoma, others addressed drugs on the horizon for SCC and data about novel therapies that may be useful in both subtypes.

Dr. Gregory J. Riely

Gregory J. Riely, MD, PhD

The Pipeline in Adenocarcinoma


Showing promise in early clinical testing is ridaforolimus, an mTOR inhibitor that targets downstream pathways of RAS, explained Gregory J. Riely, MD, PhD, associate attending in the Thoracic Oncology Service at MSKCC.

The drug is being investigated in patients whose disease is the result of mutations in KRAS, the most common driver in NSCLC (Figure), who tend to respond less vigorously to treatment than those with EGFR mutations, Riely said.

In a discontinuation trial of patients with advanced, chemotherapy-pretreated, KRAS-mutated lung cancers, Riely and coauthors demonstrated that those randomized to ridaforolimus had a 4-month median progression- free survival (PFS) versus 2 months for the placebo group, with a hazard ratio (HR) of 0.36 and a P value of .013 (J Clin Oncol. 2012;30 [suppl; abstr 7531]). The results also showed an improvement in overall survival (OS) for patients on ridaforolimus (HR = 0.47), although the P value for that endpoint was insignificant, Riely said. He added that more information will be gleaned from a larger, randomized study to be conducted by the drug’s developer, Merck.

Figure. Driver Mutations in Lung Adenocarcinoma

Driver Mutations in Lung Adenocarcinoma
Dr. Suresh S. Ramalingam

Suresh S. Ramalingam, MD


Ganetespib prevents heat shock protein 90 (HSP90) from binding to—and thus activating—oncoproteins associated with lung cancer. The drug has demonstrated activity in patients with certain driver mutations, and a phase III study of the compound versus single-agent docetaxel is being planned, according to Suresh Ramalingam, MD, chief of Thoracic Oncology and director of Medical Oncology at Emory University’s Winship Cancer Institute in Atlanta, Georgia.

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Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
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