Oncologists Still Failing 'Woefully' at Molecular Testing in Lung Cancer

Two years ago, I wrote about data showing a humbling gulf between our knowledge of molecular marker testing and our delivery of targeted therapies for advanced lung cancer. Since then, we have seen very few analyses updating the state of play, leaving us with a glimmer of hope that the oncology community is putting precision medicine into action.

But, sadly, two new analyses reveal that we're still doing a woefully poor job of offering molecular testing to our patients with advanced non–small cell lung cancer (NSCLC).

New Data

In a recent retrospective chart review from the US Oncology Network, researchers highlighted how little molecular testing in advanced lung cancer has improved. The analysis included 3474 patients with advanced NSCLC, 81% with nonsquamous histology, who underwent a workup within the 2-year period between 2018 and 2020. The investigators focused on rates of testing for PD-L1, EGFR, ALK, ROS1, and BRAF-V600E, which aside from PD-L1 all have one or more FDA-approved, and National Comprehensive Cancer Network (NCCN)-recommended, targeted therapies.

While a charitable interpreter of the results could take heart in the fact that 90% of the patients with advanced NSCLC underwent testing for at least one biomarker (most commonly PD-L1), it was disappointing to see that only 46% patients overall, and 49% of those with nonsquamous NSCLC, received testing for all five clinically relevant biomarkers. Moreover, the investigators found virtually no improvement in testing rates over the 2-year period, with the exception of testing for BRAF, which increased from 51% to 59%.

Additionally, despite the NCCN recommendations to perform next-generation sequencing (NGS) in this patient population, the researchers found that only 33% of patients received NGS during the first 6 months of the study, which ultimately increased to 45% in the last 6 months of the analysis.

Some colleagues, incredulous at the poor numbers, have asked whether a chart review could be systematically failing to track the tests being done. But a second recent analysis corroborates these testing rates. The study, which included 14,748 patients with advanced NSCLC diagnosed between January 2017 and October 2020, found that 49% of patients overall, and 53% of those with nonsquamous NSCLC, received NGS testing.

Another disconcerting finding: Black patients were significantly less likely to undergo molecular testing or enroll in clinical trials. In other words, we're also seeing racial disparities in biomarker testing.

The investigators of both studies deserve credit for helping shed light on these problems. While we can celebrate discovering new targetable mutations, such as KRAS G12C, we can't roll out the congratulatory banners if these advances are not translating into clinical practice.

Given the extent of the testing shortcomings, we need to prioritize identifying and overcoming the existing real-world barriers to molecular testing. After all, what gets measured gets done.

Several likely reasons for these shortcomings in testing include limited tissue availability, pressure to initiate treatment, and cost.

One potential solution would be to expand the use of NGS. Although plasma-based NGS testing for circulating tumor DNA is not a substitute for tissue-based molecular marker testing, it can be done immediately from any oncologist's clinic and provide results for a broader array of potentially targetable biomarkers — and does so faster than tissue testing.

Concerns surrounding cost and payer coverage are another potential issue worth tackling. These cost and coverage concerns can only be addressed if we clearly define NGS testing as a standard of care that must be covered for patients with advanced NSCLC, just as we've seen with ERBB2 testing in breast cancer.

Growing Chasm

The latest evidence cannot be ignored. These studies show that an unacceptably large fraction of patients with lung cancer are receiving what must be considered substandard care. This issue reflects a growing chasm between the focus of academic research and the way to have research translate to greatest benefit for patients. Why, for instance, are we focusing more on acquired resistance mechanisms for a driver mutation with a 2% prevalence than on the mechanisms of molecular testing that would benefit a majority of patients with lung cancer?

As the number of relevant molecular targets continues to increase — now including RET, MET, and KRAS, with new ones emerging every few months — expanding liquid biopsy molecular testing would go a long way to closing gaps in care and providing insights into the optimal treatments for each patient.

It's long past time to correct this imbalance. How do you think we should work to overcome the challenges undermining the practice of precision oncology?

H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, California, regularly comments on lung cancer for Medscape. Dr West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.

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