The Importance of Patient-Reported Outcomes in The LIBRETTO-001 Trial

Lori Wirth, MD, an associate professor of medicine at Harvard Medical School and Medical Director of the Center for Head and Neck Cancers at Massachusetts General Hospital, discusses the relevance of patient-reported outcomes (PROs) from the phase 1/2 LIBRETTO-001 study in of selpercatinib in patients with RET-altered medullary thyroid cancer (MTC) or advanced thyroid cancer.

According to Wirth, PROs were important to look at in this study due to the long-term nature of the drug. If patients were going to stay on this agent for a long time, it must be tolerable. Investigators looked at diarrhea specifically, since diarrhea is cause by a hormone, calcitonin, that is secreted by MTC.

Wirth says that for oral therapies taken daily, week after week, it’s important to take PROs into account. RET-specific inhibitors tend to be tolerable to begin with, according to Wirth. With durable responses, patients should be able to stay on the regimen for an extended period of time.

0:08 | In LIBRETTO-001, we took a look at PROs. We evaluated patients every 2 cycles for the first year, and then every 3 cycles thereafter. There were baseline PROs, as well. We looked at the EORTC QLQ-C30, and then for patients with MTC, we also carried out a study with the modified systemic therapy-induced diarrhea assessment tool. The reason that we looked particularly in the MTC patients with this 1 diarrhea-specific tool is because many patients with MTC have diarrhea that's caused by the hormone calcitonin that's secreted by MTC. In fact, 8% of patients at baseline with MTC did have diarrhea at enrollment, and a high percentage of those patients reported their diarrhea as severe at study entry. The reason why it was important, I think, however, is because we anticipated with the drug design with a RET-specific inhibitor, we should see a relatively tolerable drug for patients. We were hoping to have durable responses and hoping to have a therapy that patients are on for a long period of time. I think as we've seen in oncology, our oral therapies that are taken day in and day out every day, week after week, month after month, if there's a significant side effect profile, that can really take a toll on patients over a long period of time. Taking a look at these PROs is very important, particularly if we're claiming that a drug has a well-tolerated safety profile. I think we want to see that in PROs.