Updates on Biomarker-Directed Therapy for Solid Tumors: Focus on NTRK, RET, and NRG-1 - Episode 2

Key Considerations for Biomarker Testing

March 31, 2021
Mark A. Socinski, MD, AdventHealth Cancer Institute

Jonathan C. Trent, MD, Sylvester Comprehensive Cancer Center

Lori J. Wirth, MD, Massachusetts General Hospital

Jyoti Patel, MD, FASCO, Lurie Cancer Center at Northwestern Medicine

Benjamin P. Levy, MD, Johns Hopkins Kimmel Cancer Center

Jyoti Patel, MD, FASCO, discusses the pros and cons of tissue versus blood for molecular testing of solid tumors.

Mark Socinski, MD: I’ve found plasma-based testing for markers to be incredibly helpful clinically. Jyoti, what is your view on looking at tissue versus liquid or both in this setting, particularly when examining lung cancer?

Jyoti Patel MD, FASCO: Sure, in lung cancer, unlike some other cancers, we have a multitude of different targetable mutations. Our field has shifted in the past decade or so to support broad testing of multiple markers, as part of tissue stewardship as well as getting and answering appropriate coverage early on. I think as Ben mentioned, RNA adds another layer to that. RNA can add onto a DNA-based platform in cases in which there may be low cellularity or a large number of repetitive introns. We know, particularly with fusions, and particularly with NRG, NTRK, ROS1, that the RNA is absolutely important.

There can be other complex genetic events; there are different fusion partners, for example, that you can only assess with RNA. Our take is that all patients with advanced diseases should undergo full NGS [next-generation sequencing] that is both DNA and RNA based. Certainly, where we stand with patients with squamous tumors has evolved. Many might say that this requires a bit of a research effort because those determinations are quite infrequent. Currently, for all patients with advanced nonsquamous tumors, we sequence; we sequence for patients with squamous tumors who have no history of smoking, or low cellularity. We sequence in cases where there are admixtures or things are just poorly differentiated. Now, within our institution, Lurie Cancer Center at Northwestern Medicine, as part of a research effort, we are sequencing all patients with squamous tumors, so that pie keeps getting a little larger. At the same time, when we meet a patient, we are testing blood, and we know there is great concordance. We know that the concordance is upward of 80%, but a lot of things can change. You know that you can have insufficient tissue. You know that sometimes you will find something because of tumor heterogeneity in the blood that may not happen in the area that you biopsy, and so you make decisions based on both of them.

The real impact of this, and it’s a question that Lori and Mark touched on before, was what do you do when patients progress? You have had 1 targeted therapy, but that is really a role for rebiopsy, and often blood can be very helpful there. It can show patterns of progression as well as capture tumor heterogeneity if there is a transformation. The one piece that has changed in the treatment of lung cancer that I think we also need to acknowledge is that we now have a great TKI [tyrosine kinase inhibitor] in the adjuvant setting, so we are testing earlier and earlier. Certainly, with EGFR, we have had the approval of osimertinib for 3 years. That testing paradigm is moving up to being an option for patients with even stage I disease now.

Mark Socinski, MD: Ben kind of touched on this before; patients for whom you identify a molecular target who receive targeted therapy do so much better than those treated with standard chemotherapy approaches. This tends, at least in patients with lung cancer, not to be a group of patients who get particular benefit from immunotherapy in this setting. Like you, I bought into the idea of testing both tissue and blood at the time of diagnosis. I think that the greatest thing we can do is to identify an oncogenic driver because all those targeted agents are not available to the patient unless you make the molecular diagnosis. I think it is incredibly important to do that. I must say, the NILE trial that was published 2 years ago was very influential in convincing us that you can find things in plasma that you do not find in tissue and vice versa. No matter where you find it, you can believe it and act on it.

Transcript Edited for Clarity