Advancements in technology, endpoint selection, and patient-centered approaches are crucial for optimizing lung cancer clinical trials, according to experts at the 2024 World Conference on Lung Cancer. The discussions emphasized the importance of incorporating emerging endpoints, leveraging technology to standardize trial design, and fostering strong relationships with investigators, patients, and families.
Evolving Endpoints in Lung Cancer Trials
Historically, overall survival (OS) has been the gold standard endpoint in lung cancer trials. However, Julie Brahmer, MD, MSc, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, highlighted the advantages of using endpoints like event-free survival (EFS), disease-free survival, and pathologic complete response. EFS, for instance, is easier to measure and demonstrates efficacy earlier than OS, although its surrogacy for OS remains controversial. Pathologic complete response has shown a relationship with OS, but ongoing research is examining whether it should be viewed as a binary outcome or a continuum.
Other endpoints, such as length of delay to surgery, tumor resectability, and postoperative mortality or length of stay, are also important. Furthermore, endpoints that matter most to patients, including long-term treatment toxicities, financial burden, and time commitment, should be considered to determine optimal treatment strategies.
Brahmer emphasized the need for better technology to identify which patients benefit most from specific therapies, potentially through minimal residual disease assessment and deeper analysis of pathologic complete response and percent residual tumor volume.
Standardizing Radiotherapy with Technology
Noriko Kishi, PhD, of Kyoto University Graduate School of Medicine in Japan, stressed the importance of standardizing clinical trial design from the perspective of radiation oncologists. Variations in radiotherapy steps, from imaging to treatment planning and delivery, can threaten the validity of trial findings. Quality assurance processes to ensure compliance with radiation therapy protocols are crucial, as compliance affects OS. A study has shown that adherence to radiotherapy protocols significantly impacts patient outcomes.
Kishi noted that quality assurance efforts will need to increase with the rising frequency of imaging in new adaptive radiotherapy protocols. Artificial intelligence-based technology, such as autosegmentation, can aid in this process.
The Human Element: Relationships and Collaboration
Eric Lim, MBChB, MSc, MD, Royal Brompton Hospital, United Kingdom, shared examples of challenging clinical trials and emphasized the importance of collaboration and communication. A successful trial begins with careful planning, including selecting a principal investigator who is responsive and willing to share recognition with collaborators. The trial design should be pragmatic, fitting into a clinical pathway, and adaptive, allowing modifications based on recruitment.
Lim highlighted that factors beyond the research question, such as collaborators and global events, can influence a trial's success. He contrasted the positive experience of the VIOLET study, characterized by a simple design and a collegial group of investigators, with the challenges faced by the RAMON study, which was shut down due to low enrollment amid the COVID-19 pandemic and Brexit.
Lim concluded that "the most important component in clinical trial design and success—apart from money, which makes the world go round—is friendship and harmony."
Patient-Centered Approaches
Mary Duffy, AM, a lung cancer nurse at Peter Mac Callum Cancer Centre, Melbourne, Australia, emphasized the importance of relationships in approaching patients about clinical trial participation. Given the upheaval of a cancer diagnosis, the trial conversation should occur later, accounting for the patient's and their family's priorities. Clinical trials require significant commitments of time, travel, and money, so participation should be a well-informed decision with thorough explanations of risks and benefits.
Establishing trust through simple gestures like remembering a patient's name and using straightforward language is crucial. A therapeutic alliance based on trust, caring, and respect improves trial adherence and outcomes. Trial participation can also empower patients, giving them a sense of control over their cancer journey.
Duffy stated, "That’s very important to give patients a sense of empowerment, that they actually contribute and are in a partnership equally with the treating clinicians."
Denise Cutlip, a lung cancer patient and grant reviewer, reminded attendees of the importance of conducting effective trials that lead to impactful advances. "Nobody is more invested in your success than the patient you are looking at," she said. "We need you to succeed—it is our very lives."
