When a Promising Trial Fails, It Can Feel Personal

Mark A. Lewis, MD


February 20, 2020

This transcript has been edited for clarity.

Hello. This is Mark Lewis for Medscape.

I recently attended the Gastrointestinal Cancers Symposium. As a gastrointestinal oncologist, this may be the medical conference that I look forward to the most. Every day in my practice I see just how urgently my patients need better treatments, and they need them now. I always attend this research meeting with high hopes that new developments will emerge that I can bring back to the clinic to help my patients in real time.

This year, I went to the conference with particularly high expectations for my patients with pancreatic cancer. I don't have a favorite malignancy, but if I had to rank them, pancreatic ductal adenocarcinoma would probably be my least favorite. There is some selection bias here. I see the greatest impact on quality of life and life expectancy from this disease. I certainly lose more patients to pancreatic adenocarcinoma than to any other tumor type. It's almost as if I have a personal vendetta against it.

I also have a longstanding conception of the disease that goes back to a formative moment during my fellowship at the Mayo Clinic. We were taking care of a man in the very last stages of his illness, and he specifically requested that we attend his autopsy so that we might see how the disease ravaged him internally. Our team did attend his postmortem and, while this sounds macabre, our professor encouraged us to reach our hand into the abdominal cavity and feel the tumor. I have a model here of the pancreas; the gray appearance of this tumor very closely simulates what I saw and specifically what I felt that day—it felt like concrete.

The astrological sign for cancer is the crab. I've always thought that was apt for pancreatic cancer because the stroma around the cancer can actually feel just like a shell. I've dreamt about how I am going to crack that shell as a medical oncologist. How can I break open that almost calcified carapace and get chemotherapy inside?

I went to this year's conference hoping that we could finally break open the shell. I thought the agent most likely to do that was a drug that contains the enzyme hyaluronidase, as the shell, or the stroma, around pancreatic cancer is often rich in hyaluronic acid. HALO 109-301 is a randomized phase 3 trial of nearly 500 patients in which this enzyme was added on top of chemotherapy, which is the standard of care for advanced pancreatic cancer. It seemed quite likely that we could adapt the tumor microenvironment in a way that is favorable.

My heart sank when they showed the survival curves—there was absolutely no difference. I had tracked the progress of this research, waiting and hoping that it would yield dividends for my patients, and it was heartbreaking to see that it didn't. I think it really puts this particular hypothesis to bed.

I often tell my patients when I'm going to a conference, possibly leading them to believe that I might come back with new findings that can immediately benefit them. This time I couldn't do that. I came back to my clinic and had to admit to them that I had nothing new to offer. And, to be perfectly honest, I may have been guilty of overpromising and underdelivering.

Nonetheless, I have to applaud conferences for shining a literal and figurative spotlight on negative findings. We know that in the literature there is a publication bias toward positive results, meaning trials that move the needle in terms of practice, which is appropriate, of course.

But while we are trumpeting our triumphs, we shouldn't conceal our failures. There are multiple examples of this, and the HALO 109-301 trial is one of them. It's important that we use the podium at conferences to disseminate disappointing news about trials that didn't go as planned, because we also need to squash hype. We need to be honest when even the most biologically plausible of hypotheses don't result in positive trials. However, that doesn't mean that we should lose hope or that we should stop trying. Our patients desperately need us to continue research. We should learn from the past and try to craft a better present and future for them.

Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City, Utah. He has interests in neuroendocrine tumors, hereditary cancer syndromes, and patient-physician communication.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.