The U.S. Food and Drug Administration has granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab for use in RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed after fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy.
This is the first FDA-approved treatment for HER2-positive metastatic colorectal cancer, maker Seagen said in a Jan. 19 press release.
“Historically, patients with HER2-positive metastatic colorectal cancer who have progressed following frontline therapy have had poor outcomes. The FDA approval of a chemotherapy-free combination regimen that specifically targets HER2 is great news for these patients,” John Strickler, MD, associate professor of medicine at Duke University Medical Center, Durham, N.C., said in the press release.
Dr. Strickler was the lead investigator on the approval trial, dubbed MOUNTAINEER, which involved 84 patients who met the treatment criteria and who had also been treated with an anti-VEGF antibody. Participants whose tumors were deficient in mismatch repair proteins or were microsatellite instability–high must also have received a PD-1 inhibitor. Patients who received prior anti-HER2 therapy were excluded, the FDA explained in its own press release.
Participants were treated with tucatinib 300 mg orally twice daily– the recommended dose in product labeling – with trastuzumab administered at a loading dose of 8 mg/kg intravenously on day 1 of cycle 1 followed by a maintenance dose of trastuzumab 6 mg/kg on day 1 of each subsequent 21-day cycle.
Overall response rate was 38%, and median duration of response was 12.4 months.
The most common adverse events, occurring in at least 20% of study participants, were diarrhea, fatigue, rash, nausea, abdominal pain, infusion related reactions, and pyrexia. The most common laboratory abnormalities were increased creatinine, decreased lymphocytes, increased alanine aminotransferase, and decreased hemoglobin, among others.
Serious adverse reactions occurred in 22% of patients. The most common (occurring in ≥ 2% of patients) were intestinal obstruction (7%); urinary tract infection (3.5%); and pneumonia, abdominal pain, and rectal perforation (2.3% each). Adverse reactions leading to permanent discontinuation occurred in 6% of patients, including increased alanine aminotransferase in 2.3%.
Continued approval for the indication may be contingent upon verification and description of clinical benefit in confirmatory trials, the company said.
A global, randomized phase 3 clinical trial (MOUNTAINEER-03) is ongoing and is comparing tucatinib in combination with trastuzumab and mFOLFOX6 with standard of care and is intended to serve as a confirmatory trial, the company said.
Tucatinib is already approved in combination with trastuzumab and capecitabine for use in the treatment of advanced unresectable or metastatic HER2-positive breast cancer.
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