ALK Clinical Trials September 2024: Should Brain Metastases be Treated with Radiation at Diagnosis in ALK+ Lung Cancer? Research About a Crucial Question
For those facing the challenging diagnosis of ALK-positive lung cancer, brain metastases often pose a serious concern. Research reveals that up to 40% of these patients have brain metastases right from the start. This sets the stage for a critical question in treatment planning: Is it better to tackle these brain metastases with spot radiation, or stereotactic radiosurgery (SRS), before beginning ALK tyrosine kinase inhibitors (TKIs)? Or should we start with the TKIs and consider radiation only if necessary?
The Evolving Debate: Radiation vs. TKIs
The debate over whether to prioritize radiation or TKIs stems from the impressive advancements in ALK inhibitors. Take, for instance, the CROWN study on lorlatinib. This study has highlighted lorlatinib’s remarkable ability to penetrate the brain and control metastases effectively.
Given these promising results, many experts suggest delaying radiation in favor of initiating TKI treatment. The rationale is straightforward: these newer ALK inhibitors are proving so effective at managing brain metastases that immediate radiation might not be necessary. However, some oncologists still advocate for radiation first, arguing that it might provide more immediate control over brain lesions.
The Risks of Early Radiation
One major concern with early SRS radiation is the potential for delayed side effects. Radiation necrosis—a condition where healthy brain tissue is damaged by radiation—affects about 30% of ALK lung cancer patients who receive brain radiation. This condition doesn’t always show up right away; it can appear months or even years later, with some cases reported as long as seven years post-radiation.
While radiation necrosis often resolves without symptoms, it can lead to serious long-term issues. Neurological symptoms such as headaches, memory loss, seizures, and weakness may occur. Some of these complications may be permanent. Furthermore, the risk of radiation necrosis might be underestimated given the generally better prognosis for ALK-positive lung cancer. As survival lengthens, the likelihood of encountering radiation necrosis increases.
On the Horizon: Groundbreaking Research
To examine this debate, two major studies are currently underway—one in the USA and another in Europe. These studies are exploring the best course of action by randomly assigning participants to either receive SRS radiation before starting a TKI or to begin TKI treatment without prior brain radiation. In the US study, alectinib is being tested, while the TKI in the European study is unspecified.
The outcomes of these studies are highly anticipated, as they could set new standards for treating brain metastases in ALK-positive lung cancer. They promise to refine clinical practices and ensure that treatment recommendations are based on the latest evidence.
To learn more about these studies, click on these links: https://clinicaltrials.gov/study/NCT05522660
https://clinicaltrials.gov/study/NCT05987644
Conclusion: A Critical Decision
In 2024, second and third generation ALK TKI’s allow many patients at initial diagnosis to delay brain radiation due to their significant intracranial activity. The decision of whether to treat brain metastases with radiation before starting ALK TKI therapy remains an individual one. As research continues to unfold, the aim is to establish a more unified approach that balances optimal patient outcomes with minimized risks. Until then, patients and their healthcare teams must carefully weigh the benefits and potential risks of each treatment strategy, guided by the most current evidence and personalized patient needs.
Clinical Trials Currently Recruiting for ALK-positive Cancers.
ALK Positive, along with the University of Washington, is seeking more information about the experiences of those diagnosed with ALK-positive lung cancer. They have created a survey with many points of interest, including the experiences of those who have participated in clinical trials. The survey is confidential and approved by a research governing body. To complete the survey, please click here: ALK-positive Lung Cancer Registry and Survey
General Information About Clinical Trials
As of April 2024, there are at least 50 clinical trials that are recruiting specifically for people with ALK-positive lung cancer. Many of these trials have multiple sites worldwide. Since there are so many ALK-positive lung cancer trials, it is difficult for any one oncologist to be aware of all the trials available. You can advocate for yourself and find a clinical trial that may be a good fit for you at any juncture in treatment.
*The ALK Positive Clinical Trials Spreadsheet was developed by the ALK Positive Medical Committee. The database is updated monthly. Disclaimer: these trials have been consolidated by volunteers and should not be considered exhaustive. Listing of these trials is not an endorsement, and ALK Positive does not recommend one trial over another. Please talk with your doctor about these or any trials you are interested in.
By Ellee Urban with assistance from ChatGPT.