The RET inhibitor pralsetinib showed activity in patients with a broad variety of tumors harboring RET gene fusions, according to results from the phase I/II ARROW trial, presented by Vivek Subbiah, MD, and colleagues during the ASCO20 Virtual Scientific Program (Abstract 109).
Vivek Subbiah, MD
“This trial shows that pralsetinib has broad and durable antitumor activity across multiple advanced solid tumor types, giving it the potential to address an unmet medical need for patients with RET fusion–positive cancers,” said Dr. Subbiah, Associate Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, in a statement. “The recent tumor-agnostic drug approvals have resulted in a paradigm shift in cancer treatment, away from organ-histology–specific indications to a biomarker-guided, tumor-agnostic approach. However, until recently, we haven’t had any effective targeted therapies targeting RET alterations.”
RET fusions occur when a portion of the chromosome containing the RET gene breaks off and joins with a gene on another chromosome, creating a fusion protein capable of fueling cancer development. RET alterations are most common in medullary thyroid cancers (approximately 90% of advanced cases), papillary thyroid cancers (approximately 10%–20% of cases) and non–small cell lung cancers (approximately 1%–2% of cases).
The presentation included data for 13 patients with RET fusion–positive thyroid cancers and 14 patients with other RET fusion–positive cancers, including pancreatic cancer, cholangiocarcinoma, ovarian cancer, colon cancer, and others. Nearly all patients had stage IV disease that had progressed or relapsed on available standard therapies.
Among those patients with RET fusion–positive thyroid cancers, the duration of treatment ranged from 3 to 22 months, and 70% of responding patients remain on therapy.
Activity Seen in Multiple Tumor Types
In patients with RET fusion–positive thyroid cancer, pralsetinib achieved an overall response rate, indicating tumor shrinkage, of 91% and disease control rate, indicating tumor shrinkage or stable disease, of 100%. For all other tumor types included in the cohort, pralsetinib resulted in a 50% overall response rate and 92% disease control rate.
In other RET fusion–positive cancers, all patients with pancreatic cancer (n = 3) and cholangiocarcinoma (n = 2) in the trial had a partial response from treatment. The duration of treatment ranged from 2 to 21 months, and 67% of responding patients remain on therapy.
Further, treatment with pralsetinib was well tolerated across all patients in the cohort, explained Dr. Subbiah. “Pralsetinib was consistently safe across the overall population, and the majority of adverse events were low-grade. None of the patients in the basket cohort discontinued therapy due to treatment-related adverse events.”
Additional cohorts of the ARROW trial focus on patients with RET fusion–positive non–small cell lung cancers and RET-mutant medullary thyroid cancer. Data from the non–small cell lung cancer cohort, indicating an overall response rate of 65% and a disease control rate of 93%, were also in a poster discussion during the ASCO20 Virtual Scientific Program (Abstract 9515).
“This study stresses the importance of considering genomic testing for all patients regardless of tumor histology, so we can identify those that may benefit from targeted therapies such as pralsetinib,” said Dr. Subbiah. “It’s encouraging to be able to offer effective options to these patients and give them the gift of time.”
Disclosure: This study was funded by Blueprint Medicines. For full disclosures of the study authors, visit coi.asco.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.