Real-World Research Highlights the Importance of Targeted NSCLC Treatment

A growing awareness of unmet needs in biomarker testing and increased efforts to update national and institutional practice guidelines can shift the non–small cell lung cancer (NSCLC) treatment landscape in a direction where more patients benefit from highly effective therapies, according to Daryl Pritchard, PhD.

A poster presented at the 2022 ESMO Congress featured results from a real-world study evaluating the outcomes of patients with stage IV NSCLC with oncogenic drivers who were initially treated without TKIs. This study found that overall survival (OS) outcomes in the overall population were compromised when patients initially received chemotherapy and/or immune checkpoint inhibitors, even in those who subsequently switched to a TKI within 35 days of beginning treatment, although those patients had favorable outcomes compared with those who never received TKIs. These findings underscore the importance of performing genomic testing to determine optimal targeted therapies for NSCLC.¹

However, not all patients who are eligible for targeted NSCLC treatment receive these therapies because of gaps in clinical practice. A 2022 study detailed common reasons why the precision medicine pathway fails to retain patients throughout their treatment, many of which are factors related to the inaccessibility of biomarker test results.²

“This should be an alarm and a wake-up call to develop strategies and put them into action to address these clinical practice gaps so that we can realize the great value of TKIs and other targeted treatments,” Pritchard said.

In an interview with OncLive^®, Pritchard discussed how the findings from these studies highlight the importance of targeted therapy in advanced lung cancer, areas where the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology could be updated to better encapsulate real-world practice patterns, and the ways in which increased access to molecular testing can help usher in a new era of personalized medicine.

Pritchard is the senior vice president of Science Policy at Personalized Medicine Coalition in Washington, DC.

OncLive^®: A presentation at the 2022 ESMO Congress demonstrated the cost of forgoing targeted therapy in patients with stage IV NSCLC with oncogenic drivers. What was the significance of these findings?

Pritchard: This research was interesting, and it corroborated much of what the community was thinking. Most importantly, it shows this in a real-world evidence paradigm. These practice-based data show the great value of targeted treatments to lung cancer patients at an advanced stage. Secondly, it shows some of the clinical practice challenges, or clinical practice gaps, that are impeding the delivery of targeted therapies to patients. It highlights, or sets an alarm, that we need to address those clinical practice challenges.

What were your thoughts on this study’s findings regarding outcomes in patients who were initially treated with chemotherapy or immune checkpoint inhibitors who subsequently switched to targeted therapy?

While patients who received targeted treatments at the onset of their care fared best, [this study] showed that some of the patients who switched to a targeted therapy paradigm after they had already begun standard chemotherapy had better overall survival results than those who had never been put on the targeted treatment . That’s significant because it shows us that we must be in the mindset to get our patients to appropriate targeted therapies, even when confronted with clinical practice challenges.

If there is a problem with the turnaround time of a test or the biospecimen, and we need to re-biopsy or turn to a liquid biopsy, we should still [pursue targeted therapy]. Even though we often need to get a patient started on 1 therapy, [we should still] move them to the most appropriate therapy as soon as possible, as soon as we have the results of those tests and we know what will be the most effective treatment.

How do these findings reinforce or challenge the current NCCN guidelines?

They show that the NCCN guidelines that recommend next-generation sequencing [NGS] for advanced NSCLC are on track. [This research also showed] that many patients [without EGFR mutations who had] other biomarkers [also had] a significant improvement in OS and time to next treatment [with earlier targeted treatment].

The NCCN guideline that recommends NGS for advanced NSCLC patients is on track. [However, this research also shows that the guidelines] should be updated to reflect clinical practice. [The guidelines need to say] that if there are clinical practice challenges, if biospecimen collection is problematic, or if getting test results and interpretations is problematic, we should still pursue the targeted treatment paradigm.

Secondly, the guidelines should be updated for validated new biomarkers as they come up. [The study] made this clear [and looked at] several biomarkers, and more biomarkers are now available since the 2020 date of the data sample here. The guidelines need to be updated to show the number of biomarkers as they’re validated and useful for improving outcomes with targeted treatment.

Thirdly, other guidelines and accreditation bodies need to look at the results from this study and make moves accordingly. For example, hospitals need to see that the value of these targeted treatments is not being realized and update their institutional best practices. [Additionally, the value in] the College of American Pathologists guidelines for biospecimen processing will only be achieved if biospecimens are collected optimally and put forth into a precision oncology pathway.

What efforts within pathology could help increase the rate of molecular testing and ensure that patients who are eligible for targeted therapy are receiving it?

Clinical practice gaps are challenges that we need to overcome to realize the full value of the targeted treatment approach. [In October 2022, I] published, with a team from Diaceutics [in Belfast, United Kingdom] and Reservoir Communications Group [in Washington, DC], a paper in the Journal of Clinical Oncology Precision Oncology outlining 7 different clinical practice gaps, places where patients are falling out of the precision oncology pathway. Any oncologist or team may divide these practice gaps differently, but it provides a good landscape for where patients can drop out and what some of those challenges are.

We are finding that only about 36% of patients with advanced NSCLC are making it all the way through the precision oncology pathway. This paper is focused on [what happens] after there has been a decision for testing. [Successful biomarker testing and targeted treatment involves] acquiring test results, interpreting them [correctly], and using them appropriately. That is also indicated in the ESMO poster.

However, there are different areas. These practice challenges range from the referral for a collection of a biospecimen all the way to the treatment decision after the results come in. At each step along the way, we can lose a patient. We need to focus on a couple areas where progress can be made quickly.

The first is in pre-analytic sample processing. There are many challenges to ensuring that after a biopsy is collected, it is handled appropriately so it can be sent for testing and those test results will be accurate. Secondly, [regarding] test ordering, we need to have clinical guidelines and best practices that either require or automate the ordering of testing for biospecimens. And then, the turnaround times for those test results need to be optimized so there’s no long wait, as patients sometimes need to go on a treatment right away because they’re in an advanced cancer state. If it takes 3 or 4 weeks before results come back, that’s untenable. We need to work out that challenge. Finally, when the results are returned, they need to be usable, interpretable, and user friendly for the oncologists so they can ensure those results are applied most appropriately.

What is your main message for colleagues regarding testing within NSCLC?

This ESMO poster provides real-world, practice-based evidence for the value of a personalized medicine approach in NSCLC. The failure to fully realize that value for patients needs to be addressed. It’s clear what needs to happen.

This is a multi-stakeholder approach. We’re targeting oncologists, as they have a prominent role as the leaders in the delivery of this care. However, we need to get all the stakeholders, the pharmaceutical companies, diagnostic companies, patient advocacy groups, provider administrators, and guideline developers, together to move this forward. This isn’t [an effort] we can do in a silo. The system needs to address this to realize the value of personalized medicine.

References

1. Choksi R, Smith R, Johnson M, et al. Outcomes when stage IV non-small cell lung cancer (NSCLC-4) patients (pts) harboring oncogenic drivers (OD) are treated initially without tyrosine kinase inhibitors (TKI). Ann Oncol. 2022;33(7):S1057-S1058. doi:10.1016/j.annonc.2022.07.1233
2. Sadik H, Pritchard D, Keeling DM, et al. Impact of clinical practice gaps on the implementation of personalized medicine in advanced non-small-cell lung cancer. JCO Precis Oncol. Published online October 6, 2022. doi:10.1200/PO.22.00246