More than 130,000 new cases of colorectal cancers (CRCs) are diagnosed in the United States each year, representing 8% of all new annual cancer cases. The rate of patients with CRC surviving more than five years is 65.1%; however, patients with metastatic disease (mCRC) have a poorer prognosis, with only 13.5% surviving more than years. As many as 40% of patients with mCRC remain candidates for third-line therapy, with some patients requiring up to five lines of therapy because of drug resistance.
Lonsurf® (trifluridine and tipiracil) is an oral antitumor nucleoside indicated for the treatment of mCRC in patients who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an antivascular endothelial growth factor biologic therapy, and, if RAS wild-type, an antiepidermal growth factor receptor therapy.
During a product theater at the 42nd Annual Congress in Denver, CO, Elizabeth Prechtel Dunphy, MSN, CRNP, AOCN®, from the Abramson Cancer Center at Penn Presbyterian Medical Center in Philadelphia, PA, gave an overview of the drug and what nurses need to know when managing a patient with mCRC.
The recommended starting dose for trifluridine and tipiracil is 35 mg/m2, up to a maximum of 80 mg per dose administered orally twice daily within one hour of a meal on days 1–5 and 8–12 of each 28-day cycle until disease progression or unacceptable toxicity. “Without food, it can reduce neutrophil counts,” Dunphy cautioned. Doses should be rounded to the nearest 5 mg increment.
“It is very important to obtain blood count to monitor for severe myelosuppression,” Dunphy said. Trifluridine and tipiracil should not be initiated until the patient has an absolute neutrophil count (ANC) ≥ 1,500/mm3, a platelet count ≥ 75,000/mm3, and grade 3 or 4 nonhematologic adverse events (AEs) resolved to grade 0 or 1. Treatment should be held if ANC is < 500/mm3, platelets are < 50,000/mm3, or if grade 3 or 4 nonhematologic AEs occur. “Ideally, [you want to] dose delay before dose reduce,” Dunphy said. After recovery, trifluridine and tipiracil can be resumed after reducing the dose by 5 mg/m2 per dose, for a maximum of three dose reductions to a minimum dose of 20 mg/m2 twice daily. Trifluridine and tipiracil should not be escalated once it has been reduced.
Trifluridine and tipiracil has a warning for severe myelosuppression and embryo-fetal toxicity. And it is a cytotoxic drug, “so educate patients on handling and disposal of this product,” Dunphy cautioned.
The U.S. Food and Drug Administration’s approval of trifluridine and tipiracil was based on results of the international, randomized, double-blind, placebo-controlled, phase III RECOURSE study that included 800 adult patients with previously treated CRC who were randomized 2:1 based on KRAS status (wild-type versus mutant), time since diagnosis of first metastasis (< 18 versus ≥ 18 months), and region (Japan versus United States, Europe, and Australia) to receive trifluridine and tipiracil plus best supportive care (n = 534) or placebo plus best supportive care (n = 266).
Patients were included if they received at least two prior lines of standard chemotherapy for mCRC, had an Eastern Cooperative Oncology Group performance status score of 0 or 1, had absence of brain metastasis, and had absence of ascites requiring drainage in the past four weeks. The median patient age was 63 years, 61% were male, and 58% were Caucasian.
The median overall survival (primary endpoint) was statistically significantly improved (hazard ratio [HR] = 0.68; 95% CI = 0.58–0.81; p < 0.001) in those receiving trifluridine and tipiracil (7.1 months; 95% CI 6.5–7.8) compared to those receiving placebo (5.3 months; 95% CI = 4.6–6.0). The median progression-free survival was also improved (HR = 0.47; 95% CI = 0.40–0.55; p < 0.001). The median duration of response was 12.7 months in the trifluridine and tipiracil group and 6.8 months in the placebo cohort.
The most common any-grade AEs included asthenia/fatigue (52% in trifluridine and tipiracil group versus 35% in placebo cohort), nausea (48% versus 24%), decreased appetite (39% versus 29%), diarrhea (32% versus 12%), and vomiting (28% versus 14%). Hematologic toxicities were increased in the trifluridine and tipiracil cohort. Infections also occurred more frequently in trifluridine and tipiracil-treated patients (27%) compared to those receiving placebo (15%). “Even in this heavily pretreated population, AEs were fairly tolerable with dose delays,” Dunphy said.
Trifluridine and tipiracil was associated with severe and life-threatening myelosuppression, including anemia (18%), neutropenia (38%), thrombocytopenia (5%), and febrile neutropenia (3.8%). One patient (0.2%) died because of neutropenic infection. In addition, 9.4% of patients treated with trifluridine and tipiracil received granulocyte-colony stimulating factors (G-CSFs). “In my experience [with the drug], I have not had to use G-CSF in our patients,” Dunphy said.
Most patients in the study (86%) did not require a dose reduction; however, 3.6% of patients discontinued trifluridine and tipiracil because of AEs. Among the 13.7% of patients who required a dose reduction, the most common reasons were neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea.
Deaths were reported in 68% of the trifluridine and tipiracil group (n = 364) and 79% of the placebo group (n = 210).
Dunphy concluded the presentation by providing tips to help patients take the medication as prescribed, including:
- Patient education: Patient retention for new therapies is low, and education needs to be reinforced throughout the course of therapy. She advised to “speak their language. For example, they do not know what ‘palliative’ means.” Go over goals of therapy, planned duration of treatment, potential short- and long-term AEs, and guidance on storage, handling, administration, and disposal of the drug.
- Communication: This is key to being on the same playing field with patients. Communication should be clear and concise and provided to patients in written or electronic form, tailored to patients’ education level. She advised that patients have a 24/7 point of contact for any problems and to provide this information in the initial patient visit.
- Tracking/monitoring: Create a treatment calendar or patient diary and follow up to make sure they are taking their medication as required, Dunphy said.
- Reminders: Use timers, clocks on phones, or alarms to remind patients about treatment.
- Caregivers: Keep them involved, because they often remind patients to make sure they took their medication. “Include them in discussions from the beginning,” Dunphy advised.
Refer to the prescribing information and important safety information for trifluridine and tipiracil for more information.
This program was supported by Taiho Oncology.