The investigational RET inhibitor pralsetinib (BLU-667) has demonstrated durable activity, regardless of RET fusion genotype, in multiple advanced solid tumor types, according to data from the phase I/II ARROW trial (Abstract 109). Earlier analyses showed a treatment effect in the phase II cohorts with RETfusion–positive non–small cell lung cancer and RET mutation–positive medullary thyroid cancer.
During the ASCO20 Virtual Scientific Program, Vivek Subbiah, MD, of The University of Texas MD Anderson Cancer Center, presented results from the ARROW basket cohort of patients with other RET fusion–positive solid tumors; these patients had been treated with 400 mg of oral pralsetinib once daily. The primary endpoints were the centrally reviewed overall response rate (ORR; per RECIST version 1.1 criteria) and safety.
As of the data cutoff of February 13, 2020, 27 patients were enrolled, 13 (48.1%) with RET fusion thyroid cancer (12 papillary thyroid carcinoma, one poorly differentiated thyroid cancer) and 14 (51.9%) with other RET fusion solid tumors—three colon, three mixed histology lung, three pancreatic, two cholangiocarcinoma, one neuroendocrine, one ovarian, and one thymus—all “hard-to-treat epithelial tumor types,” Dr. Subbiah said.
All but one patient (96.3%) had stage IV disease and had received prior systemic therapy. Twelve of the patients with RET fusion thyroid cancer (92.3%) had received radioactive iodine treatment, and all 14 patients with other RETfusion tumors had received chemotherapy.
The duration of treatment was up to 23.5 months, with a median relative dose intensity of 96% (range, 58-150). Pralsetinib demonstrated clinical activity in RET fusion–positive thyroid cancer (ORR 91%) and other RET fusion–positive tumor types (ORR 50%; Table).
After presenting two case studies of his patients treated with pralsetinib, Dr. Subbiah noted that “these are some of the cases and patients that make a phase I investigator wake up and go to the clinic in the morning.”
Safety findings from this cohort were similar to those seen in the overall trial population of 354 patients. The most frequently reported treatment-related adverse events (in at least 15% of patients) were anemia (33%), increased aspartate aminotransferase (33%), decreased white blood cell count (33%), hypertension (30%), increased alanine aminotransferase (26%), hyperphosphatemia (19%), and neutropenia (19%). Most adverse events were grade 1 or 2 (per the Common Terminology Criteria for Adverse Events), and no patients discontinued the trial due to treatment-related adverse events.
“Pralsetinib has broad and durable antitumor activity with multiple advanced solid tumors,” Dr. Subbiah said in his concluding remarks. “Cancer is a genetic disease, and if we are serious about treating cancer, we need to have every bit of intelligence, and genomics should be a part of therapy.”
“Cancer is a genetic disease, and if we are serious about treating cancer, we need to have every bit of intelligence, and genomics should be a part of therapy.” – Dr. Vivek Subbiah
Discussant Mark A. Lewis, MD, of Intermountain Healthcare, is an oncologist, survivor of neuroendocrine cancer, and patient advocate. He shared Dr. Subbiah’s enthusiasm for the ARROW trial results.
“As a patient with a rare disease myself, it is so unbelievably heartening to see that we are no longer an afterthought to the big four cancers of lung, breast, colon, and prostate,” Dr. Lewis said.
“As a patient with a rare disease myself, it is so unbelievably heartening to see that we are no longer an afterthought to the big four cancers of lung, breast, colon, and prostate.” – Dr. Mark A. Lewis
He also suggested that clinicians should discuss next-generation sequencing results with their patients, as the volume of information regarding cancer genomics may be overwhelming to them.
“Driver mutations are indeed breaking down traditional histopathologic boundaries, and patients will increasingly define themselves by their therapeutic targets,” Dr. Lewis said.
The ARROW study is ongoing and continues to enroll patients with various RETfusion–positive solid tumors. Additional data from the trial were presented during the ASCO20 Virtual Scientific Program (Abstract 9515).
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου