The broad impact of real-world evidence is on (virtual) display at ASCO20

The use of PD-L1 as a predictive marker for immuno-oncology therapies in NSCLC is still a field in flux, with complex FDA-approved indications depending on line of therapy and histology. This RWE study contributes to the current state of clinical knowledge, underscoring that histologic subtype is one of the most relevant practical decision points used in interpreting molecular test results and making treatment choices.

While this is still exploratory work, it displays the importance of real-world evidence in the study of rare patient populations. Determining whether all BRCA alterations are equal in their response to targeted therapies will be critical in finding the best treatment courses for individual patients.

The current state of affairs in clinical trial participation is suboptimal, and it behooves the clinical research community to understand the dynamics of trial accrual and how they may ultimately impact research success. This study shows that the stringency of clinical eligibility criteria greatly reduces the pool of patients able to participate in clinical research, and lends urgency to the general efforts currently underway to address this issue.

Oncology clinics often anticipate that participation in clinical studies is associated with daunting staff workload increases. By automating time-consuming manual steps in the trial conduct process, tools such as this can make trial participation a more approachable undertaking, particularly for community sites. Increasing the number of clinics willing to become clinical trial sites could improve clinical research access and participation.

Reducing the intensity of EOL care is a goal of quality-of-care initiatives. While immune checkpoints have become a major breakthrough across multiple tumor types, this RWE study may point to an unintended consequence of their therapeutic profile: favorable tolerability and high expectations for effectiveness. Namely, the tendency to use immunotherapy in EOL settings where less aggressive approaches may be preferable. RWE continues to be a source of insights into patterns of care, providing us with the tools to identify unexpected trends and address potentially detrimental practices.

Full-fledged prospective trials are needed to generate major pivotal clinical evidence. However, some research questions may be addressed without the need of a full trial deployment, via novel approaches that leverage routine care infrastructure. This study explores that paradigm, with an innovative prospective strategy that leverages the efficiency of real-world data collection, strengthening aspects such as completeness and data capture quality.

The tumor-agnostic approval of pembrolizumab based on the presence of the MSI-H marker represented a watershed moment in which traditional disease definitions were bypassed with one single approval. This RWE study helps us understand the clinical and practical meaning of that approval, as it provides validation of the registrational trial data in a unique multi-tumor setting where additional trials would be challenging to conduct.

The availability of EGFR TKIs with different activity patterns spurs the need to identify and understand the potential clinical relevance of subsets of patients with EGFR mutant NSCLC with different mutation profiles. This study shows how a clinico-genomic database can be a powerful tool in identifying these ultra-rare patient groups and gaining insights on their clinical outcomes.