Entrectinib Yields Durable Responses, Manageable Safety in NTRK Fusion-Positive Gastrointestinal Cancers

Ignacio Garrido-Laguna, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, discusses findings from an updated integrated analysis exploring entrectinib in patients with NTRK fusion-positive gastrointestinal cancer, demonstrating durable responses and manageable safety across tumor types with a longer follow-up.

These findings were presented at the 2022 ESMO World Congress on Gastrointestinal Cancer in Barcelona, Spain.

Transcript:

Good morning. I'm Ignacio Garrido-Laguna from Huntsman Cancer Institute, the University of Utah in Salt Lake City. We're here at World GI Congress in Barcelona. We have presented today updated efficacy and safety data with entrectinib, an NTRK inhibitor in patients with NTRK-positive gastrointestinal cancers. The data we presented today comes from three small trials that enrolled several hundred patients with different tumor types, NTRK-positive. Today we're focusing on the GI cancer patient population.

Our data included both safety and efficacy data. As you know, NTRK fusions are present in small number of patients across different tumor types. In particular, in GI cancers we see these fusions in less than 1% of the patients. The efficacy data we presented today included 16 patients. The safety data we presented showed that entrectinib is safely tolerated. The most common adverse events were weight gain, diarrhea. Most of them were Grade 1 or 2. The most common Grade 3 adverse event was weight gain.

In terms of the efficacy data that was presented today, as I mentioned, 16 patients with different tumor types, most of the patients had colorectal cancer. These were 10 patients. We had 4 patients with pancreatic cancer and 1 patient each with cholangiocarcinoma or adenocarcinoma of the upper GI tract. The response rate for the overall cohort of GI cancer patients was around 40%. The response rate for the pancreatic cancer cohort was 75%. Three out of 4 patients responded. The response rate for the colorectal cancer cohort was lower than for the overall cohort. Two of 10 patients responded to therapy with an overall response rate of around 20%. The patient with adenocarcinoma of the GI tract had a complete response and the patient with cholangiocarcinoma also had a partial response.

Duration of response was around 20 months. Progression-free survival was around 7 months and the overall survival in this cohort of patients was 4 months longer than previously reported. Looking at specific tumor types, the colorectal cancer success showed lower response rate compared to the overall cohort, around 20% versus 44%. And it also showed shorter progression-free survival of 3 months compared to the overall cohort of 7 months.

The conclusion is that this data reinforces the concept that entrectinib is safe in this patient population. It has shown that activity responses are durable. The caveat is that these are still a very small subset of patients, less than 1%. Some data that we did not present today addresses  the percentage of these patients that had mismatch repair deficiency. We know this from other data. Most patients with colorectal cancer with NTRK fusions will also have mismatch repair deficiency between 50, 75%. I think that it's an overview of the data we presented today. I hope you enjoy this data and I look forward to the next time.

Source:

Garrido-Laguna I, Lonardi S, Bazhenova L, et al. Entrectinib in NTRK fusion-positive gastrointestinal cancers: Updated integrated analysis. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract SO-32.