ASCO RWE Research

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

Last updated: January 4, 2021

  • neal_02

    Neal Meropol, MD

    Vice President, Head of Medical and Scientific Affairs

Collectively, Flatiron’s presentations at this year’s American Society of Clinical Oncology Annual Meeting (ASCO20) display the broad impact of EHR-derived real-world evidence (RWE) across the oncology therapeutic lifecycle: from discovery through development and, ultimately, in support of patient care.

Highlights include the exploration of genomic biomarkers and their relationship to real-world outcomes; the use of EHRs to enable prospective data collection through a novel approach to the execution of clinical trials by linking real-world clinico-genomic, imaging and outcomes data; efforts to leverage our provider network to understand barriers to clinical trial participation and apply machine learning technology to streamline patient ascertainment; and finally, the role of real-world data in understanding treatment patterns, with attention on rare populations and end-of-life care.

Flatiron’s research collaborators include partners from academia, life sciences companies and most notably for 2020, our valued community practice partners. Our research presentations span multiple applications with one specific objective in mind: to learn from the experience of every cancer patient.

Below are highlights from a series of Flatiron-authored posters. Visit the ASCO Virtual Scientific Program to see six additional posters featuring Flatiron real-world data.

Research Focus

Biomarkers that predict who may benefit from targeted treatments

PD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous NSCLC

Deborah Doroshow et al.

Deborah Doroshow et al.

This study explored the predictive value of PD-L1 tumor proportion score on non-small cell lung cancer (NSCLC) tumor cells as a biomarker for response to pembrolizumab in advanced squamous versus non-squamous cancers in 1560 patients. Results suggest that PD-L1 may not be an appropriate predictive biomarker for checkpoint inhibitor use in NSCLC with squamous histology.

Why this matters

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.

View the full poster on the ASCO website
pdl-1
Overall survival of patients with PD-L1 positive (≥50%) and negative (<50%) squamous and non-squamous NSCLC
Hear Deborah Doroshow, MD, PhD, of the Tisch Cancer Institute, explore the differential value of PD-L1 tumor proportion score as a predictive biomarker for overall survival after first-line pembrolizumab NSCLC patients.

This study explored the predictive value of PD-L1 tumor proportion score on non-small cell lung cancer (NSCLC) tumor cells as a biomarker for response to pembrolizumab in advanced squamous versus non-squamous cancers in 1560 patients. Results suggest that PD-L1 may not be an appropriate predictive biomarker for checkpoint inhibitor use in NSCLC with squamous histology.

Why this matters

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.

View the full poster on the ASCO website
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Association of BRCA alteration type with real-world outcomes to PARP inhibitors in patients with metastatic castrate-resistant prostate cancer

Emmanuel S. Antonarakis et al.

Emmanuel S. Antonarakis et al.

Researchers tested the hypothesis that patients with tumors harboring BRCAdel may have prolonged benefit from PARP inhibitors (PARPi) treatment compared to those harboring other BRCA alterations, since tumors with homozygous deletions would be unable to develop acquired resistance to PARPi therapy.

Why this matters

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.

View the full poster on the ASCO website
BRCA-1
Time to treatment discontinuation and overall survival from start of PARPi in BRCAdel patients vs. BRCAother patients

Researchers tested the hypothesis that patients with tumors harboring BRCAdel may have prolonged benefit from PARP inhibitors (PARPi) treatment compared to those harboring other BRCA alterations, since tumors with homozygous deletions would be unable to develop acquired resistance to PARPi therapy.

Why this matters

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.

View the full poster on the ASCO website
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Research Focus

Barriers (and solutions) to clinical trial participation

Use of real-world data to understand barriers to interventional clinical trial enrollment in community oncology clinics

Johnetta Blakely et al.

Johnetta Blakely et al.

There are limited data from community oncology clinics on the degree to which common trial exclusion criteria and socioeconomic factors play a role in low enrollment rates. Researchers explored the impact of labs, performance status, and race on clinical trial eligibility and accrual, and found that exclusion criteria and other known barriers challenge the ability for community oncology clinics to recruit representative patient populations.

Why this matters

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.

View the full poster on the ASCO website
Blakely et al
The prevalence of exclusion criteria in patients on various lines of therapy.
Listen to Johnetta Blakely, MD, of Tennessee Oncology, discuss the findings of this research, which sought to understand the barriers to interventional clinical trial enrollment in community oncology clinics.

There are limited data from community oncology clinics on the degree to which common trial exclusion criteria and socioeconomic factors play a role in low enrollment rates. Researchers explored the impact of labs, performance status, and race on clinical trial eligibility and accrual, and found that exclusion criteria and other known barriers challenge the ability for community oncology clinics to recruit representative patient populations.

Why this matters

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.

View the full poster on the ASCO website
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An automated EHR-based tool for identification of patients with metastatic disease to facilitate clinical trial patient ascertainment

Jeffrey Kirshner et al.

Jeffrey Kirshner et al.

Efforts to rapidly identify patients for clinical trials in routine practice, including automation of patient ascertainment from electronic health record (EHR) data, are hindered by the lack of information on metastatic status in structured format. In collaboration with community oncology clinic partners, researchers developed a machine learning tool that infers metastatic status from unstructured EHR data with high accuracy.

Why this matters

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.

View the full poster on the ASCO website
Kirshner et al
Metastatic status classification of 200 patients using machine learning tool and after user review.
Jeffrey Kirshner, MD, of Hematology-Oncology Associates of Central New York, explains a machine learning tool developed to help facilitate clinical trial patient ascertainment.

Efforts to rapidly identify patients for clinical trials in routine practice, including automation of patient ascertainment from electronic health record (EHR) data, are hindered by the lack of information on metastatic status in structured format. In collaboration with community oncology clinic partners, researchers developed a machine learning tool that infers metastatic status from unstructured EHR data with high accuracy.

Why this matters

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.

View the full poster on the ASCO website
View more arrow_viewmore_02

Research Focus

Understanding treatment patterns at the end of life

The adoption of immune checkpoint inhibitors and patterns of care at the end of life

Fauzia Riaz et al.

Fauzia Riaz et al.

As aggressive therapy at end of life (EOL) is associated with increased costs and patient distress, researchers examined the association between the FDA approvals of immune checkpoint inhibitors (ICIs) and treatment patterns at EOL in patients with advanced melanoma, non-small cell lung cancer (NSCLC) (cancer types with an ICI indication), or patients with microsatellite stable colon cancer (a cancer type without an ICI indication). The adoption of ICIs was associated with a substantive increase in the use of systemic therapy at EOL in melanoma, and a smaller yet significant increase in NSCLC.

Why this matters

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.

View the full poster on the ASCO website
Riaz et al.
Change in the use of immune-checkpoint inhibitors and any systemic therapy across pre- and post-FDA approval time periods for each cancer type at the end of life.

As aggressive therapy at end of life (EOL) is associated with increased costs and patient distress, researchers examined the association between the FDA approvals of immune checkpoint inhibitors (ICIs) and treatment patterns at EOL in patients with advanced melanoma, non-small cell lung cancer (NSCLC) (cancer types with an ICI indication), or patients with microsatellite stable colon cancer (a cancer type without an ICI indication). The adoption of ICIs was associated with a substantive increase in the use of systemic therapy at EOL in melanoma, and a smaller yet significant increase in NSCLC.

Why this matters

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.

View the full poster on the ASCO website
View more arrow_viewmore_02

Research Focus

Novel clinico-genomic platforms for discovery

A multi-stakeholder platform to prospectively link longitudinal real-world clinico-genomic; imaging; and outcomes data for patients with metastatic lung cancer

Michael W. Lu et al.

Michael W. Lu et al.

This study presents a multi-stakeholder platform to prospectively collect and link real-world clinico-genomic, imaging, and outcomes data to longitudinal blood-based genomic testing in 1,000 patients with lung cancer across 20 community oncology and academic practices. The objectives are to evaluate both the feasibility of building a scalable, prospective platform, and the associations between circulating tumor DNA and real-world clinical outcomes, including overall survival.

Why this matters

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.

View the full poster on the ASCO website
M Lu et al
An overview of the sources of data. Listen to the audio clip below for more information.
Lee Schwartzberg, MD, of West Cancer Center, describes a multi-stakeholder platform to prospectively collect and link real-world clinico-genomic, imaging, and outcomes data to longitudinal blood genomic profiling for patients with lung cancer.

This study presents a multi-stakeholder platform to prospectively collect and link real-world clinico-genomic, imaging, and outcomes data to longitudinal blood-based genomic testing in 1,000 patients with lung cancer across 20 community oncology and academic practices. The objectives are to evaluate both the feasibility of building a scalable, prospective platform, and the associations between circulating tumor DNA and real-world clinical outcomes, including overall survival.

Why this matters

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.

View the full poster on the ASCO website
View more arrow_viewmore_02

Characteristics and outcomes of real-world patients with microsatellite instability-high solid tumors treated with pembrolizumab monotherapy after FDA approval

Novel clinico-genomic platforms for discovery

Novel clinico-genomic platforms for discovery

As tumor-agnostic therapies are a new paradigm, it is important to assess their use and effectiveness in routine clinical practice. Researchers examined the use of pembrolizumab in a tumor-agnostic study of 129 microsatellite instability-high (MSI-H) patients across 33 tumor types using a real-world clinico-genomic database.

Why this matters

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.

View the full poster on the ASCO website
Snow et al
Overall survival and time to treatment discontinuation in patients with MSI-H solid tumors receiving pembrolizumab monotherapy in real-world care.
Flatiron Health's Tamara Snow discusses the background of this study and how patients with MSI-H solid tumors responded to pembrolizumab in real-world care.

As tumor-agnostic therapies are a new paradigm, it is important to assess their use and effectiveness in routine clinical practice. Researchers examined the use of pembrolizumab in a tumor-agnostic study of 129 microsatellite instability-high (MSI-H) patients across 33 tumor types using a real-world clinico-genomic database.

Why this matters

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.

View the full poster on the ASCO website
View more arrow_viewmore_02

Real-world outcomes for advanced non-small cell lung cancer patients with EGFR exon 19 deletions stratified by deletion size

Sai-Hong I. Ou et al.

Sai-Hong I. Ou et al.

EGFR exon 19 deletions (x19dels) are well-established targetable drivers in non-small cell lung cancer (NSCLC). Historically, x19dels have been treated as a single group, but it is unclear whether responses vary for distinct subtypes. A real-world clinico-genomic database was used to compare demographic, clinical and genomic characteristics, as well as outcomes to EGFR tyrosine kinase inhibitors (TKIs) for advanced NSCLC patients with x19dels of varying lengths.

Why this matters

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.

View the full poster on the ASCO website
ex19del
Real-world progression-free survival and overall survival from start of any first-line EGFR TKI in EGFR ex19del-5 and ex19del-other patients

EGFR exon 19 deletions (x19dels) are well-established targetable drivers in non-small cell lung cancer (NSCLC). Historically, x19dels have been treated as a single group, but it is unclear whether responses vary for distinct subtypes. A real-world clinico-genomic database was used to compare demographic, clinical and genomic characteristics, as well as outcomes to EGFR tyrosine kinase inhibitors (TKIs) for advanced NSCLC patients with x19dels of varying lengths.

Why this matters

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.

View the full poster on the ASCO website
View more arrow_viewmore_02

Visit the ASCO Virtual Scientific Program to see six additional posters featuring Flatiron real-world data.