Bridging Clinical Trials and Real-World Evidence in ALK-Positive Non–Small Cell Lung Cancer Treatment: Part 2
Key Takeaways:
- Time-to-treatment discontinuation (TTD) can serve as a real-world benchmark alongside progression-free survival, offering clinicians a more realistic lower-bound estimate of treatment effectiveness outside clinical trials.
- Pathway decisions should extend beyond efficacy, incorporating tolerability, access to therapy, and supportive care—particularly in community settings with more complex, comorbid patient populations.
- Real-world evidence helps validate and contextualize trial findings, supporting more balanced, evidence-based decision-making by showing how treatments perform across broader, more representative patient populations.
In Part 2 of our discussion with Rahul Mudumba, PhD, MHS, University of Southern California, we explore how real-world metrics such as TTD can complement traditional clinical trial endpoints when informing value-based decision-making for ALK-positive NSCLC. Mudumba highlights how these data can guide pathway development in community oncology settings, where patient complexity and resource constraints play a critical role, and emphasizes the importance of balancing real-world evidence with trial data.
How should pathway developers weigh TTD alongside traditional trial endpoints when making value-based decisions?
Rahul Mudumba: It serves as a benchmark. The progression-free survival or the numbers you see in the clinical trial represent an upper bound. You could talk about it as such and as an ideal scenario.
The TTD or real-world estimates can be what you could expect in the real world, whether as a lower bound or a more realistic assumption. In reality, it might fall somewhere in between. The trial might tell you the best case, ideal scenario in the real world. TTD output might be a more pessimistic or realistic scenario of what happens when you administer these drugs among more representative patient populations.
How might these findings influence pathway decisions in community oncology settings, where resource constraints and patient comorbidities may impact sequencing?
Rahul Mudumba: It's not just the efficacy in a first-line setting that we see in a clinical trial in an ideal circumstance. Pathways should also emphasize tolerability, quick access to therapy, and supportive care. Patients benefit from these expensive but effective therapies in ways that cannot be looked at in a narrow sense.
So, we have to take a more comprehensive approach to how we develop pathways with tolerability and access in mind, alongside promising efficacy.
Is there anything else you hope audiences will take away from this study?
Rahul Mudumba: One takeaway is that real-world evidence or observational research is not the enemy of clinical trials. It could be seen as a complement or a supplement to clinical trials. Clinical trials answer very important questions and provide clean estimates, but maybe they lack generalizability.
Real-world evidence loosens some of the strict assumptions that the clinical trial imposes and then helps us see if the same findings hold in the real world. The results are not as lenient or extreme in the real world, which is expected to be the case, but it helps bolster confidence that the trial findings could hold in a more representative population.
Going forward, balancing the weight of evidence between the two and complementing trial evidence with real-world evidence will lead to better decision-making for patients.
Can you tell us a bit about your upcoming study and how it builds on the real-world evidence you’ve already presented on first-line ALK inhibitor use?
Rahul Mudumba: The findings we presented at the American Society of Clinical Oncology (ASCO) were a small portion of the previous work that we also published in the Journal of Managed Care Pharmacy. In that study, we looked at treatment patterns, overall survival, and TTD in a first-line setting.
The work that is under peer review is now a larger real-world study where we are employing quasi-experimental methods to mitigate confounding and derive a cleaner comparison of what the most effective drug is in the first line. By using state-of-the-art methods in a larger sample size, we've found that alectinib emerges superior to crizotinib, but lorlatinib offers substantive benefit to alectinib too. We also looked at the largest real-world patient population in the US to date. It will be an exciting study once we get it past the peer review line.
