We Need to Level With Our Patients About the Benefits of Tumor Sequencing

Kathy D. Miller, MD


August 27, 2021

This transcript has been edited for clarity.

This is Dr Kathy Miller from Indiana University. Today I want to discuss the amazing revolution we have all witnessed over the past 10 years or so. We now commonly sequence patients' tumors with the hope that tumor sequencing will find actionable mutations and point to different treatments, and that our patients will benefit from this exercise.

I want to point you to an important piece of work in the April edition of JAMA Oncology. This comes from Arul Chinnaiyan's group at the University of Michigan, and the lead author is Dr Erin Cobain. They looked at their experience from 2011 to 2018, sequencing tumors from 1138 patients with metastatic disease. Their question was simple: Is this beneficial? Do patients benefit from tumor sequencing?

In their abstract, they suggest that 37% of patients achieved a benefit, meaning their disease was stable or responding for 6 months or more. And 19% of patients achieved benefit lasting more than 12 months. That caught my attention because it certainly doesn't match my experience in this field. So I delved more into the details, and when I look at their numbers, that's not what I see. They started with sequencing 1138 patients; 49 patients were responding or stable at 6 months. That's not 37% of 1138; that's 4%. At 12 months, 26 patients achieved benefit. That's not 19%; that's 2%.

How did we come to such a different conclusion? Well, they decreased the denominator. They started with 1138. Some of those had sequencing technical failures. Of those they were able to sequence, there was a potentially actionable mutation in 817. Of those, 132 were treated, and that's the denominator they used for benefit — only those patients who actually received treatment. I don't believe that's fair. I think that's lying to ourselves and to our patients, because all 1138 patients agreed to biopsy and sequencing with the hope that they would get treatment and get benefit, but they didn't. The benefit to the whole population was 4% at 6 months and 2% at 12 months. Now, I'm not suggesting that this means we should stop sequencing patients' tumors and stop work in this field. But I do believe it means that we need to have different conversations with our patients so that they understand the real likelihood that they personally, with their disease, will benefit from this endeavor.

I found one other piece of important information in this work. When we use tumor sequencing to focus on identifying treatments, it can also point to germline mutations. The authors found germline mutations in 14% of their overall population, and in at least 4% of those patients — 49 of the total — those germline mutations had potential therapeutic relevance, mainly for patients who had germline BRCA mutations who could potentially benefit from PARP inhibitors. That germline information was very important for those 14% of patients and their families. That not only means we need to pay attention to those results in our patients who have tumor sequencing, but it's another call to consider broadening our criteria for offering germline testing to patients with cancer, focusing less on family history, which doesn't identify all of our patients who have germline mutations.

Take a look at this paper. See what you think about the numbers. Challenge yourself to think about how you talk about sequencing to your patients with metastatic disease.

Kathy D. Miller, MD, is associate director of clinical research and co-director of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University. Her career has combined both laboratory and clinical research in breast cancer.

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