– Combination regimen is approved for use in the second-line treatment setting and beyond –
“Historically, patients with HER2-positive metastatic colorectal cancerHER2-positive metastatic colorectal cancer who have progressed following frontline therapy have had poor outcomes,” said John Strickler, M.D., associate professor of medicine, Duke University Medical Center, and lead investigator for the MOUNTAINEER trial. “The FDA approval of a chemotherapy-free combination regimen that specifically targets HER2 is great news for these patients.” “Biomarker testing is bringing new hope to people living with some types of colorectal cancer by opening the door to targeted treatments like TUKYSA for those who have RAS wild-type, HER2-positive diseaseHER2-positive disease,” said Michael Sapienza, CEO, Colorectal Cancer Alliance. “It is critical that physicians and patients understand the importance of comprehensive biomarker testing at diagnosis because it can inform treatment decisions and help improve outcomes.” Results from the MOUNTAINEER trial showed a 38% overall response rate (ORR) (95% Confidence Interval [CI]: 28, 49) per blinded independent central review (BICR) in the patients who received TUKYSA in combination with trastuzumab (N=84 with a median age of 55.0 years [range: 24 to 77]). Complete responses were observed in 3.6% of patients (n=3), and partial responses were observed in 35% of patients (n=29). The median duration of response (DOR) per BICR was 12.4 months (95% CI: 8.5, 20.5). At study entry, 64% and 70% of these patients had liver or lung metastases, respectively. The Prescribing Information for TUKYSA includes warnings and precautions for diarrhea, hepatotoxicity and embryo-fetal toxicity, some of which may be severe or fatal. In MOUNTAINEER, serious adverse reactions occurred in 22% of patients; the most common (in ≥2% of patients) were intestinal obstruction (7%), urinary tract infection (3.5%), pneumonia, abdominal pain and rectal perforation (2.3% each). The most common adverse reactions (≥20%) in patients treated with TUKYSA and trastuzumab were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions and pyrexia. Adverse reactions leading to permanent discontinuation of TUKYSA occurred in 6% of patients; the most common (in ≥2% of patients) was increased alanine aminotransferase (ALT) (2.3%). Please see additional Important Safety Information below. The FDA’s Accelerated Approval Program allows for approval of a medicine based on a surrogate endpoint that is reasonably likely to predict clinical benefit if the medicine fills an unmet medical need for a serious condition. A global, randomized phase 3 clinical trial (MOUNTAINEER-03) is ongoing and will compare TUKYSA in combination with trastuzumab and mFOLFOX6 with standard of care, which is intended to serve as a confirmatory trial and potentially support future global regulatory submissions. Merck, known as MSD outside of the U.S. and Canada, is commercializing TUKYSA in regions outside of the U.S., Canada and Europe and plans to discuss results from the MOUNTAINEER trial with certain health authorities as it continues to accelerate the filing of TUKYSA in its territories. MOUNTAINEER is a U.S. and European open-label, multicenter phase 2 clinical trial of TUKYSA in combination with trastuzumab that evaluated 84 patients with HER2-positive, RAS wild-type, unresectable or metastatic colorectal cancerHER2-positive, RAS wild-type, unresectable or metastatic colorectal cancer following previous standard-of-care therapies. Patients evaluated in MOUNTAINEER had not received prior anti-HER2 therapy. Patients received TUKYSA (300 mg) twice per day orally in combination with trastuzumab intravenously (8 mg/kg loading dose, then 6 mg/kg every three weeks thereafter) until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (BICR) according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1. Important Safety Information
In HER2CLIMB, serious adverse reactions occurred in 26% of patients; the most common (in ≥2% of patients) were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock. Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; the most common (in ≥1% of patients) were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; the most common (in ≥2% of patients) were hepatotoxicity (8%) and diarrhea (6%). The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia and rash. In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed. In MOUNTAINEER, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were decreased lymphocytes, decreased sodium, increased AST, and increased bilirubin. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible in 87% of patients with values outside normal lab limits upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed. Use in Specific Populations
For more information, please see the full Prescribing Information for TUKYSA here. Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company’s marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter. 1 American Cancer Society: Key Statistics for Colorectal Cancer. https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html. Accessed January 2023. 2 Wang J., et al. Metastatic patterns and survival outcomes in patients with stage IV colon cancer: A population‐based analysis. Cancer Med. 2020 Jan; 9(1): 361–373. 3 Ahcene Djaballah S, Daniel F, Milani A, Ricagno G, Lonardi S. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target. Am Soc Clin Oncol Educ Book. 2022;42:1-14. doi:10.1200/EDBK_351354.