Caitlin Douglass

found that an epidermal growth factor receptor (EGFR), erlotinib, was well tolerated in combination with whole-brain radiation therapy (WBRT) for patients with brain metastases from nonsmall cell lung cancer (NSCLC).

Through the phase II trial, researchers examined the use of erlotinib with WBRT in an effort to extend survival time for patients with NSCLC, which was based on the understanding that activated

&rsquo;s contribute to radiation resistance. In patients with NSCLC, brain metastases are the leading cause of death.

Lung cancer continues to be the leading cause of cancer-related mortality among men and women. In the United States an estimated 222,520 newly diagnosed lung cancer cases are diagnosed each year. Prognosis for advanced lung cancer remains grim for patients with NSCLCabout 20% to 40% of patients with NSCLC develop brain metastases at some point during their prognosis.

Current treatment options for brain metastases among patients with NSCLC include WBRT, stereotactic radiosurgery, and surgical resection or some combination thereof; however, median survival time for patients who seek WBRT generally range anywhere from 3 to 6 months depending upon individual age, performance, and the location of metastatic lesions.

In the phase II trial, median overall survival (OS) rate for study participants was 11.8 months. The OS rates for the 6-month mark, the 1-year mark, and the 2-year mark were found to be 68%, 50%, and 24%, respectively.

The study, conducted by the University of Arizona and the MD Anderson Cancer Center of The University of Texas&nbsp;examined 40 patients who were given a loading dose of erlotinib for 6 days and then a dose of erlotinib per day concurrently with WBRT. Following whole-brain radiation therapy, patients received maintenance erlotinib until the disease progressed or until adverse events became intolerable for the patient.

Additionally, researchers found a particular benefit for patients with

mutations. Previous studies have indicated that

mutations can be found in about 10% to 15% of patients with NSCLC, yet researchers found the rate to have nearly tripled to 50% in the studied patient group.

mutation testing has been commonplace in diagnosing and treating NSCLC, for which patients are stratified depending upon their levels of mutation. This study supports the notion that mutation status seems to have a strong correlate response to anti

mutations have a &ldquo;different biologic profile or path of spread than do wild-type

tumors.&rdquo; Studies suggest that tumors with a predominantly mesenchymal phenotype do not respond as well to EGRF-targeting agents as do tumors with a stronger epithelial phenotype. As a result, patients with

mutations may be more prone to brain metastases than patients without mutated tumor types.

&ldquo;Although these findings are thought provoking, they must be interpreted cautiously because of the small numbers of patients and lack of randomization,&rdquo; the authors wrote in their report. The researchers added that the study could also have been impacted by a negative selection bias, because MD Anderson only treats patients with four or fewer CNS lesions with a stereotactic approach and because of the changing use of erlotinib in treatment since the beginning of the study.

Erlotinib is currently approved for use in initial treatment for patients with a new diagnosis of

-mutated lung cancer, which researchers warned would likely lead to different outcomes than those found with patients in the phase II trial.

&ldquo;This trial of concurrent erlotinib and radiation therapy for the initial treatment of brain metastases from NSCLC showed that this combination was safe and well tolerated,&rdquo; the authors added. &ldquo;Survival times for all patients in this trial exceeded those expected from historical controls, and the benefits seemed exceptionally high for patients with

Welsh J, Komaki R, Amini A et al. Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer.

. 2013;31(7):895-902. doi:10.1200/jco.2011.40.1174.

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A study published in the Journal of Clinical Oncology found that an EGFR inhibitor, erlotinib, was well tolerated in combination with whole-brain radiation therapy for patients with brain metastases from NSCLC.

New Options Possible in Patients With NSCLC and Brain Metastases

Researchers discovered that the use of anamorelin among patients with advanced nonsmall cell lung cancer considerably helped more patients stabilize or gain lean body mass, a factor that consequently enables patients with cachexia to survive longer.

The study results of the ROMANA phase III study were presented at the International Association for the Study of Lung Cancer&rsquo;s 16th World Conference on Lung Cancer (WCLC) in Denver.

The data further supported previous findings that demonstrated a positive correlation between the cancer drug and increased lean body mass.

Previous presentations at the ESMO 2014 and ASCO 2015 meetings detailed the ROMANA I and ROMANA II study findings, demonstrating an increase in lean body mass during treatment with anamorelin. Serious drug-related adverse events (AEs) affected less than 3% of the patients involved in the studies.

The findings presented at WCLC further reinforce anamorelin&rsquo;s positive connection to weight gain in patients with NSCLC. According to the presentation, a greater percentage of patients demonstrated a maintained or increased lean body mass compared with placebo in both studies. When both study results were explored together, overall survival (OS) significantly increased among patients who were able to stabilize or increase their lean body mass.

Researchers asserted that anamorelin&rsquo;s affect on body weight allows patients who face both NSCLC and cachexia to survive longer. Patients battling cancer often experience symptoms of anorexia, which entails loss of appetite and inevitably decreased body mass. However, treatment options for cachexia and anorexia are very limited.

Greater body mass and especially lean body mass play a critical role in helping cancer patients achieve healthier levels during treatment stages. These findings regarding anamorelin use among patients with NSCLC showed that its treatment can produce a significant impact in patient palliative care.

Anamorelin is an investigational, orally active ghrelin receptor agonist that is targeted to treat symptoms of cachexia, anorexia, and unexpected weight loss in patients with NSCLC. Though the novel drug is not yet approved by any regulatory body, the drug is designed to stimulate multiple pathways to positively regulate body weight, lean body mass, appetite, and metabolism.

In doing so, maintained or increased body weight has the potential to increase a patient&rsquo;s life expectancy considerably as demonstrated by the findings presented in September at the WCLC.

These latest findings originated from the ROMANA I and ROMANA II studies, which were two international, double-blind, phase III trials that each examined nearly 500 patients. Study participants either received the cancer drug or a placebo orally over a 12-week period, which was determined at a random 2:1 ratio by the study researchers. Patients were able to continue chemotherapy treatment during the trial.

According to the report, researchers were first able to measure co-primary endpoints over the 12-week trial period by change in lean body mass and handgrip strength from baseline. The secondary endpoints consisted of the change in body weight, anorexia symptoms, and 1-year OS of participants in both studies. Additionally, there were few drug-related adverse events, the only most common of which was hyperglycemia among patients.

Helsinn.com. Additional data for anamorelin in ROMANA 1 and ROMANA 2 studies | Helsinn Corporate. 2015. http://www.helsinn.com/news/additional-data-for-anamorelin-in-romana-1-and-romana-2-studies/. Accessed October 9, 2015.

Researchers discovered that the use of anamorelin among patients with advanced non-small cell lung cancer considerably helped more patients stabilize or gain lean body mass, a factor that consequently enables patients with cachexia to survive longer.

Caitlin Douglass | Authors

Articles

New Options Possible in Patients With NSCLC and Brain Metastases

Anamorelin Shows Increased Survival in Non-Small Cell Lung Cancer