Regulatory Decision Summary for Lonsurf
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
Taiho Inc. filed a submission for market authorization for Lonsurf (Trifluridine/tipiracil hydrochloride) for the treatment of metastatic colorectal cancer in patients who have received prior treatment with standard therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy and who are refractory to or intolerant of those therapies.
Why was the decision issued?
An overall survival (OS) benefit of Lonsurf plus best supportive care as compared to placebo plus best supportive care has been demonstrated in Study TPU-TAS-102-301 (RECOURSE), a multinational, large (n = 800), randomized, double blind, placebo controlled trial. In the RECOURSE study population patients had received at least 2 prior regimens of therapy and were refractory to or intolerant to the standard therapies after each of their last prior administration (fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab for patients with wild-type RAS). A statistically significant overall survival benefit was observed with Lonsurf as compared to placebo: HR = 0.68 [95% CI: 0.58, 0.81; p-value <0.0001]. The median OS was 7.1 months in the Lonsurf arm as compared to 5.3 months in the placebo arm, a difference of 1.8 months.
The safety data from a total of 761 patients included 533 patients from RECOURSE Study treated with Lonsurf and 265 patients treated with placebo. The most frequently reported toxicities associated with Lonsurf treatment were gastrointestinal, hematologic disorders and decreased appetite. The reported hematologic toxicities were often severe and life threatening (grades 3 and 4) and included neutropenia (37.9%), leukopenia (21.4%), anemia (18.2%), thrombocytopenia (5.1%) and febrile neutropenia (3.8%). One patient died due to neutropenic infection considered related to Lonsurf treatment. Toxicities were managed with dose reductions and treatment discontinuations. Hospitalizations were not increased with Lonsurf treatment as compared to placebo. With dose modifications, patients were able to continue on treatment with Lonsurf longer than with placebo. The Product Monograph (PM) of Lonsurf contains boxed warnings on myelosuppression and GI toxicity. Additional risks have been labeled in the PM. Because of the safety profile, Lonsurf is not indicated in patients with moderate and severe hepatic impairment. Lonsurf is not indicated in patients with severe renal impairment (creatinine clearance below 30 mL/min). Lonsurf has not been studied and therefore has not been recommended for treatment in children (<18 years of age). Lonsurf is not recommended in pregnant and nursing women.
The risks identified with Lonsurf have been labelled in the PM. The benefit risk profile is considered favorable for the indicated population.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| LONSURF | 02472104 | TAIHO PHARMA CANADA, INC. | TIPIRACIL (TIPIRACIL HYDROCHLORIDE) 6.14 MG TRIFLURIDINE 15 MG |
| LONSURF | 02472112 | TAIHO PHARMA CANADA, INC. | TIPIRACIL (TIPIRACIL HYDROCHLORIDE) 8.19 MG TRIFLURIDINE 20 MG |