D. Ross Camidge, MD, PhD, is a professor of medicine-medical oncology, and director of the Thoracic Oncology Clinical Program and Clinical Research Program at the University of Colorado Cancer Center – Anschutz Medical Campus.

D. Ross Camidge, MD, PhD, Director, Thoracic Oncology Clinical Program, University of Colorado Cancer Center, discusses the use of crizotinib as a ROS1 inhibitor in non-small cell lung cancer (NSCLC).

ROS1 is a gene rearrangement that is structurally-related and similar to ALK, but is more rare. ROS1 rearrangements occur in about 1% of NSCLC cases but is also present in gallbladder cancer and colorectal cancer. Camidge points out that there is only a certain number of things to drive a cancer and though frequency will vary, researchers and physicians study the same drivers more often.

Crizotinib is so structurally related to ALK, making it an adequate ROS1 inhibitor as well. A 50-60% response has been observed and Camidge says that it could be a better ROS1 inhibitor than an ALK inhibitor.

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Dr. Camidge on Crizotinib as a ROS1 Inhibitor in NSCLC

D. Ross Camidge, MD, PhD, director of the Thoracic Oncology Clinical Program at the University of Colorado Cancer Center, discusses the selective administration of targeted therapies in the adjuvant setting for patients with non-small cell lung cancer (NSCLC).

In the phase II SELECT study, 36 patients with stage I-III 

 mutation-positive NSCLC received adjuvant treatment with the EGFR TKI erlotinib, following completion of standard adjuvant treatments. After 2 years, treatment with erlotinib was discontinued. The initial disease-free survival (DFS) rate was 94%, which seems impressive, Camidge states; however, after 3 years DFS dropped to around 60% and at 4 years it was 40%.

Overall, these findings suggest that adjuvant use of EGFR-targeted treatments is not killing cancer cells in the same fashion as chemotherapy. As in advanced NSCLC, these agents seem to control the disease but, due to toxicity and costs, lifetime treatment with these agents is not an option.

Since sensitive cells survive, merely targeting cells that illicit growth is not sufficient, Camidge suggests. As a result, researchers must pinpoint the genes that allow cancer cells to enter a "siege" state that allows them to survive these treatments. Once found, it is likely that synthetic lethal approaches will be required to maximize the cancer kill rate. However, until these new agents are found, Camidge does not believe targeted therapies should be used in the adjuvant space to treat NSCLC.

D. Ross Camidge, MD, PhD, from the University of Colorado Cancer Center, discusses the selective administration of targeted therapies in the adjuvant setting for patients with non-small cell lung cancer.

Dr. Camidge on Targeted Therapies in Adjuvant NSCLC

The ever changing and evolving world of molecular-based clinical cancer research has created serious patient enrollment issues, explains D. Ross Camidge, MD, PhD, director of the Thoracic Oncology Clinical Program at the University of Colorado Cancer Center.   

Camidge believes that finding patients with a sufficient level of a molecular abnormality is becoming difficult, especially as more is understood about heterogeneity. Moreover, geographical diversity adds further difficulty to adequate enrollment for trials that focus on treating one exact genetic abnormality.  

Several online resources exist for distilling enrollment information, Camidge explains. The first preexisting resource mentioned is clinicaltrials.gov, which was recently redesigned to improve the discoverability of information. The website offers a search function and useful information on clinical trials but is not specifically geared toward patients. 

Patient focused websites and online resources represent a budding and successful area for patient enrollment. 

As an example, Camidge touts the success of the expert moderated forums provided by the Global Resource for Advancing Cancer Education (GRACE), founded by H. Jack West, MD. Early in the development of the ALK-targeted agent crizotinib, Camidge participated in a podcast with West that was very successful at providing information on the now approved agent. 

As an earlier example of using the Internet for recruitment, Camidge describes the successes of the noted researcher George D. Demetri, MD, from the Dana-Farber Cancer Institute. Demetri used online resources for patient enrollment in a gastrointestinal stromal tumor trial, for which the National Institutes of Health did not believe he could find an adequate patient population. 

Despite these successes there are still disconnects between the 21st century communication needed for enrollment and the 20th century methods of conducting trials. As a result, Camidge feels more needs to be done to improve how clinical trials are conducted with more of an emphasis on local laboratories and telemedicine. Additionally, Camidge notes that clinical trial locations need to be dispersed throughout the United States, rather than localized to urban centers.

D. Ross Camidge, MD, PhD, from the University of Colorado Cancer Center, discusses the ever changing and evolving world of clinical cancer research.

Dr. Camidge on the Evolution of Clinical Cancer Research

D. Ross Camidge, MD, PhD, director of the Thoracic Oncology Clinical Program at the University of Colorado Cancer Center, discusses two circumstances that may warrant performing a second molecular test for the same abnormalities in a patient with lung cancer. 

If a tumor develops an acquired resistance to therapy, resequencing may detect if a new secondary mutation is responsible. For instance, patients with an activating mutation in 

 who develop resistance to a targeted tyrosine kinase inhibitor, such as erlotinib, may harbor a new mutation in 

Additionally, Camidge explains that it may be necessary to retest a patient if they do not respond appropriately to therapy. If a patient who tests positive for an 

 mutation does not respond to crizotinib, a mistake may have been made. Resequencing helps rule out any mistakes or errors that may have been made during the first test.

Dr. Ross Camidge, from the University of Colorado Cancer Center, Discusses Resequencing Lung Cancer

D. Ross Camidge, MD, PhD

Articles

Dr. Camidge on Crizotinib as a ROS1 Inhibitor in NSCLC

Dr. Camidge on Targeted Therapies in Adjuvant NSCLC

Dr. Camidge on the Evolution of Clinical Cancer Research

Dr. Camidge Discusses Resequencing Lung Cancer