STARLET Collaboration Aims to Improve NSCLC Treatments

Non-small-cell lung cancer (NSCLC) is a type of lung cancer that can have changes in a specific gene called the epidermal growth factor receptor (EGFR). These changes often lead to better treatment responses when patients are given certain medicines known as EGFR tyrosine kinase inhibitors (TKIs). Many patients with advanced NSCLC may develop Brain Metastases (BM), which means the cancer has spread to the brain. Studies suggest that patients with EGFR mutations may be at a higher risk of developing these brain issues because they tend to live longer after treatment.

#Treatment Options

One common treatment for brain metastases is called stereotactic radiosurgery (SRS). This method delivers a high dose of radiation very precisely to the brain with minimal impact on surrounding tissues. Research has found that adding SRS in the treatment of patients with brain metastases, especially if they have only one or a few lesions, can lead to better overall survival and prolonged independence in daily activities. Because of the side effects associated with whole brain radiation, SRS has now become the preferred method for treating multiple brain metastases.

When it comes to treating NSCLC with brain metastases, Osimertinib is a newer drug that targets the mutated EGFR. It is known to penetrate the brain effectively and is considered more effective than older EGFR TKIs. The U.S. Food and Drug Administration (FDA) has approved it for treating patients with certain types of EGFR mutations, both as a first line and second line treatment option.

Some clinical trials have shown that patients with stable and symptom-free brain metastases treated with Osimertinib had a significantly longer time without growth of the brain disease compared to those treated with older drugs. However, the actual effectiveness of Osimertinib in the brain is still somewhat uncertain since many trial participants had received prior brain radiation.

#Current Research

The best way to combine SRS and Osimertinib for patients with untreated brain metastases from EGFR mutant NSCLC is not clearly defined. Guidelines suggest that in certain cases, local treatments can be delayed for patients who have asymptomatic brain metastases. However, the evidence behind this recommendation is weak.

There are conflicting results from past studies. Some researchers found that patients who received radiation earlier had better survival than those who started with an EGFR TKI and delayed radiation. In contrast, other studies did not find any difference in outcomes.

To clarify the best approach, two recent randomized controlled trials (RCTs) are looking into whether using SRS followed by Osimertinib works better than just using Osimertinib alone. Each of these trials has a small number of participants and is mainly aimed at gathering initial data to inform future larger studies.

#STARLET Collaboration

To further this research, a new collaboration called STARLET has been formed. This collaboration will conduct an extensive review and analysis combining data from the two trials mentioned earlier. The goal is to compare the effectiveness of SRS followed by Osimertinib against Osimertinib alone in controlling brain metastases in patients.

#Methodology

The STARLET collaboration will include only randomized controlled trials so that the results are as reliable as possible. Participants must be receiving Osimertinib either as their first or second treatment. This includes newly diagnosed patients with specific EGFR mutations and brain metastases, as well as those who developed brain issues while on earlier treatments.

All trials must have received ethical approval, and patients must have given their consent to participate. This ensures that the rights and well-being of all participants are protected.

#Data Collection

The data collection process will involve securely sharing individual patient data from the included studies. The information will be kept confidential and de-identified to protect patient privacy. The data will be stored in a secure database and will be checked for accuracy and consistency.

#Assessing Bias and Quality

The quality of the included studies will be evaluated to check for any biases that might affect the results. This includes examining how participants were chosen for the trials, whether they were treated fairly, and if the results were reported honestly.

#Outcomes of Interest

The main outcome this collaboration will look at is the time without growth of brain disease at 12 months after treatment. Secondary outcomes include overall survival, time until other types of brain treatment are needed, quality of life, and the occurrence of any significant side effects.

#Subgroup Analyses

The analysis will also explore whether certain groups of patients respond better to one treatment over the other. Key factors may include the type of EGFR mutation, the number of brain metastases, age, and overall health before starting treatment.

#Data Analysis

A detailed analysis plan will be created and agreed upon by all members of the STARLET collaboration before starting the data analysis. This will ensure that the analysis is carried out consistently and thoroughly.

The primary outcome of time without brain disease growth will be analyzed using statistical methods to account for other factors that may affect results. Other secondary outcomes will be examined using various statistical models.

#Ethical Considerations

All trials contributing to the STARLET collaboration must have received ethical approval, and patients must have provided informed consent. This ensures that the study is conducted ethically and responsibly. The individuals who ran the original trials will maintain control over their data, which will be shared only in a de-identified format.

#Publication Plans

Results from this research will be shared publicly once the analysis is complete. The collaboration aims to publish findings under the name of the group, ensuring that all contributors receive appropriate credit for their work.

#Conclusion

The STARLET collaboration aims to provide new insights into the best treatment strategies for patients with EGFR mutant NSCLC who develop brain metastases. By combining data from multiple studies, the collaboration hopes to improve patient outcomes and ultimately guide future clinical practices. The results could determine whether a larger Phase III study is needed to further clarify the best treatment options for this challenging condition.