Alectinib halts lung cancer growth more than a year longer than crizotinib

Findings from a phase III clinical trial point to a more effective initial treatment for patients with ALK-positive non-small cell lung cancer (NSCLC). Compared to the current standard of care crizotinib (Xalkori), the newer ALK inhibitor alectinib (Alecensa) halted cancer growth for a median of 15 months longer and caused fewer severe side effects.

The study was featured in a press briefing today and presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.

“This is the first global study to compare alectinib with crizotinib in ALK-positive lung cancer and establishes alectinib as the new standard of care for initial treatment in this setting,” said lead study author Alice T. Shaw, MD, PhD, Director of Thoracic Oncology at Massachusetts General Hospital Cancer Center in Boston, MA. “Alectinib was especially beneficial in controlling and preventing brain metastases, which can have a major impact on patients’ quality of life.”

About 5% of NSCLCs are ALK-positive, meaning they have a genetic rearrangement where the ALK gene is fused with another gene. In the United States, about 12,500 people are diagnosed with ALK-positive NSCLC each year.

Crizotinib, the first medicine to specifically target ALK, was approved by the FDA in 2011. Although the majority of patients initially benefit from crizotinib, the cancer typically starts growing again within a year. Alectinib is a more potent, next-generation inhibitor of ALK. It was initially approved in 2015 for use in patients with advanced NSCLC that worsens despite crizotinib.

“The fact that this second-generation targeted treatment halted advanced lung cancer growth for more than two years while preventing brain metastases is a remarkable result in this difficult disease,” said ASCO Expert John Heymach, MD, PhD. “Thanks to this advance, we are on the road to helping these patients live longer and better.”

About the Study

In this open label clinical trial (ALEX), researchers randomly assigned 303 patients with stage IIIB or IV, ALK-positive NSCLC to receive alectinib or crizotinib. The patients had not received prior systemic therapy for advanced NSCLC.

Key Findings

Alectinib reduced the risk of cancer progression or death by 53% compared with crizotinib. Based on independent review, alectinib extended the median time to progression by about 15 months (median progression-free survival was 25.7 months with alectinib and 10.4 months with crizotinib).

“Nobody imagined it would be possible to delay advanced lung cancer progression by this much. Most targeted therapies for lung cancer are associated with a median progression-free survival of roughly 12 months,” said Dr. Shaw.

While both treatments cross the blood-brain barrier, alectinib was more effective in preventing brain metastases than crizotinib, because it can better penetrate into the brain. At 12 months, the incidence of brain metastases was much lower with alectinib than with crizotinib (9% vs. 41%).

Overall, severe side effects were less common with alectinib than with crizotinib, occurring in 41% vs. 50% of patients. The most common side effects of alectinib were fatigue, constipation, muscle aches, and swelling, whereas crizotinib caused gastrointestinal problems and liver enzyme abnormalities.

Next Steps

The researchers will continue to follow patients on this study to see if those treated with alectinib live longer than those treated with crizotinib. Meanwhile, several ongoing clinical trials are comparing other next-generation ALK inhibitors to crizotinib in the first-line setting.

Research suggests possible new treatment for EGFR-positive lung cancer

Findings from a phase III clinical trial point to a potential new treatment for patients newly diagnosed with advanced, epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC). Compared to the EGFR inhibitor gefitinib (Iressa), one of the standard targeted medicines for this disease, second-generation EGFR inhibitor dacomitinib delayed cancer growth by a median of 5.5 months more.

The study was featured in a press briefing and presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.

Each year, about 140,000 people worldwide (15,000 in the United States alone) are diagnosed with EGFR-positive NSCLC. EGFR-positive cancers have genetic changes that lead to an overactive EGFR protein, which fuels the growth of cancer cells. EGFR tyrosine kinase inhibitors (TKI) are the standard treatment for people with newly diagnosed EGFR-positive NSCLC. This study is the first phase III head-to-head comparison of two EGFR TKIs.

“We changed the treatment paradigm for EGFR-positive lung cancer a few years ago when targeted therapy replaced chemotherapy,” said lead study author Tony Mok, MD, a professor and chair of the Department of Clinical Oncology at the Chinese University of Hong Kong. “This study shows that dacomitinib may be an even more effective treatment for these patients. However, patients should be aware of the need to deal with potential side effects when making treatment decisions.”

“It’s been nearly 15 years since EGFR-targeted therapies were introduced, helping extend survival for thousands of patients in the time since. The second generation of these therapies is more effective, but can also cause greater side effects, so patients and their doctors will need to weigh the risks and benefits,” said ASCO Expert John Heymach, MD, PhD.

Due to its chemical properties, dacomitinib blocks EGFR more effectively than first-generation inhibitors, such as gefinitib and erlotinib, and this explains its ability to keep tumor growth in check longer. On the other hand, this also leads to stronger suppression of the normal EGFRs in healthy tissues, causing more side effects such as skin rash, acne, and diarrhea.

About the Study

In this phase III clinical trial, researchers randomly assigned 452 patients newly diagnosed with IIIB or IV, EGFR-positive NSCLC to receive dacomitinib or gefitinib. The patients were enrolled in Asia and Europe.

Key Findings

Patients who received dacomitinib had a 41% lower chance of cancer progression or death than those who received gefitinib. The progression-free survival was 14.7 months with dacomitinib, compared to 9.2 months with gefitinib. Longer follow up is needed to assess the median overall survival.

The most common severe (grade 3) side effects of dacomitinib were acne (in 14% of patients) and diarrhea (in 8% of patients). The dose of daconitinib was lowered in about 60% of patients due to side effects. Liver enzyme abnormalities were the most common severe (grade 3) side effect of gefitinib (in 8% of patients).

“Dacomitinib is a more potent, second-generation EGFR inhibitor that shares the issue of increased side effects in the skin and gastrointestinal tract, like afatinib (Gilotrif). In spite of this, the activity seen in this study should allow for consideration of this effective therapy in this patient population,” said Dr. Mok. Another second-generation EGFR inhibitor, afatinib, is already FDA approved as an initial treatment for EGFR-positive NSCLC. Dacomitinib is not yet approved for any indication.

Long Term Survival Indicated for Advanced Stage Colorectal Cancer Patients who Survive at Least Two Years

Improvements in chemotherapy and liver surgery have resulted in increased overall survival in patients with advanced stage colorectal cancer in recent decades. In order to better predict outcomes for these patients, researchers at Rutgers Cancer Institute of New Jersey conducted a retrospective analysis and found that stage IV colorectal cancer patients who survived at least two years have a better prognosis than originally thought. Results of the work will be presented as part of a poster presentation at the American Society of Clinical Oncology Annual Meeting being held in Chicago early next month.

“With patients in this population living longer, it is imperative we refine prognostic information to more accurately predict survival.  This data will assist multi-disciplinary cancer management teams in making treatment decisions that ultimately will impact a patient’s quality of life,” notes Darren Carpizo, MD, PhD, surgical oncologist and director of the Hepatobiliary Program at Rutgers Cancer Institute and senior investigator of the work (pictured).

Investigators examined data on more than a thousand stage IV colorectal cancer patients seen at Rutgers Cancer Institute between 2005 and 2015. This included patients who had their cancer removed through surgery and were treated with follow-up therapies, as well as those patients who were not eligible for surgery. Complete data was available for 125 patients who survived for more than two years (75 had surgical removal of their cancer; 50 did not).  Median overall survival of patients who underwent surgery was not reached, while median overall survival for those who were not eligible for surgery was six years and three months.

“For those patients not eligible for initial surgery who survive two years, these findings indicate they may benefit from future surgery, if feasible, to treat remaining disease. For those patients who initially had surgery, this information may be helpful to identify patients who might benefit from repeat surgery to resect any recurrent metastatic disease,” adds Dr. Carpizo, who is also an associate professor of surgery and pharmacology at Rutgers Robert Wood Johnson Medical School.

Rutgers Cancer Institute of New Jersey (www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center. As part of Rutgers, The State University of New Jersey, Rutgers Cancer Institute is dedicated to improving the detection, treatment and care of patients with cancer, and to serving as an education resource for cancer prevention both at its flagship New Brunswick location and at its Newark campus at Rutgers Cancer Institute of New Jersey at University Hospital. Physician-scientists across Rutgers Cancer Institute also engage in translational research, transforming their laboratory discoveries into clinical practice that supports patients on both campuses.