Impact of Molecular Testing on Lung Cancer Survival: Real-world Insights


A comprehensive study on the association between the availability of molecular genotyping results and overall survival in advanced non-squamous, non-small cell lung cancer patients, shedding light on the importance of timely and concurrent testing.


Melina E. Marmarelis, MD: Charu, I’m curious if you can walk people through some of our thought processes surrounding the paper we’re going to talk about, in particular how we were thinking about molecular testing. We obviously feel strongly that it’s a good thing for our patients, but I wanted to ask that question and probe into it a little bit more. Can you talk about the real-world cohort study?

Charu Aggarwal, MD, MPH: Absolutely. This is a work you’re very familiar with since we partnered on this very closely. This was our paper in JCO Precision Oncology this summer that evaluated the association between the availability of molecular genotyping results and overall survival [OS] in patients with advanced nonsquamous, non–small cell lung cancer [NSCLC]. We’ve talked a lot about how current guidelines recommend that these patients be tested. However, the association between the availability of results and OS is really not known.

We’ve shown earlier that if you layer in plasma testing or liquid biopsy to tissue sequencing, you can dramatically increase the ability to detect molecular alterations. We’ve shown this earlier that you can really increase the number of patients that benefit from targeted therapy just by introducing liquid biopsy, which is minimally invasive and has a good turnaround. But really what’s not known…[is] does this availability of results impact survival? And that was really our goal and question. So, we conducted a real-world cohort study using electronic health records in patients with newly diagnosed metastatic nonsquamous NSCLC, which will be our patient population. And we looked at the association between survival, test results, and availability. But we also looked at the comprehensiveness of test results.

It’s one thing to test, but it’s another thing to do comprehensive testing. We wanted to look at the association between the availability of results as well as whether it was done by tissue and plasma or both. Do we get results faster if we do concurrent plasma and tissue testing, for example? So we looked at our institutional University of Pennsylvania experience because we’ve really embraced concurrent genotyping ever since we published in 2018. So, we had real-world data on a large number of patients. We looked at 326 patients who were truly [treatment]-naive and newly diagnosed. Among these patients, we found that 80% of the patients, which I think is incredible for a large organization such as ours…did have results available prior to initiation of first-line therapy and 20% did not.

When we looked at OS, patients within the available testing group had significantly longer survival with a hazard ratio of 0.43. And this is incredible because if this was a drug, this would probably get the presidential plenary at a symposium. But this is the simple act of testing a patient. This is a simple act of having those results available and looked at. And this can impact survival. This held true in multiple covariate analyses while we adjusted for age, sex, race, etc. The adjusted odds of availability of results before the first-line therapy was higher with concurrent tissue and plasma testing vs tissue testing alone. In fact, we were twice as likely. So, our adjusted odds ratio was about 2. We were twice as likely to get these results back faster if we did concurrent tissue and plasma testing, I think primarily because of the fact that plasma results come back quickly. But we also found that when plasma wasn’t back, the tissue did give us an answer, and I think this is really important data that shows us 2 things.

One is that just getting results back can be linked to OS. So if you don’t have results back, you cannot extend the ability to offer personalized therapy; thereby, you’re restricting an OS advantage. So I think the first is OS and the second is that by using a concurrent approach, we are able to begin treatment much faster. I think this is something that we’ve embraced at our program and continue to do so that we can extend this across not just our institution, but across our health system.

Melina E. Marmarelis, MD: That’s great. I think it’s important to point out this is one step over the process, saying that getting molecular testing leads to better survival. There’s ongoing work and there’s work out of Canada to show that that’s also a cost-effective approach, because you can avoid unnecessary immunotherapy in patients for a target is found. So [these are] some really exciting results.

Transcript edited for clarity.

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