Lonsurf Adverse Reactions

Summary of safety profile: The most serious observed adverse drug reactions in patients receiving Lonsurf are bone marrow suppression and gastrointestinal toxicity (see Precautions).
Lonsurf as monotherapy: The safety profile of Lonsurf as monotherapy is based on the pooled data from 1114 patients with metastatic colorectal or gastric cancer in controlled phase III clinical studies.
The most common adverse drug reactions (≥30%) are neutropenia (53% [34% ≥Grade 3]), nausea (31% [1% ≥Grade 3]), fatigue (31% [4% ≥Grade 3]) and anaemia (30% [11% ≥Grade 3]).
The most common adverse drug reactions (≥2%) that resulted in treatment discontinuation, dose reduction, dose delay, or dose interruption were neutropenia, anaemia, fatigue, leukopenia, thrombocytopenia, diarrhoea and nausea.
Lonsurf in combination with bevacizumab: The safety profile of Lonsurf in combination with bevacizumab is based on the data from 246 patients with metastatic colorectal cancer in the controlled phase III clinical study (SUNLIGHT).
The most common adverse reactions (≥30%) are neutropenia (69% [48% ≥Grade 3]), fatigue (35% [3% ≥Grade 3]), and nausea (33% [1% ≥Grade 3]).
The most common adverse reactions (≥2%) that resulted in treatment discontinuation, dose reduction, dose delay, or dose interruption of Lonsurf when used in combination with bevacizumab were neutropenia, fatigue, thrombocytopenia, nausea and anaemia.
When Lonsurf is used in combination with bevacizumab, the frequency of the following adverse reactions was increased compared to Lonsurf as monotherapy: neutropenia (69% vs 53%), severe neutropenia (48% vs 34%), thrombocytopenia (24% vs 16%), stomatitis (11% vs 6%).
Tabulated list of adverse drug reactions: The adverse drug reactions observed from the 533 treated patients with metastatic colorectal cancer in the placebo-controlled Phase III (RECOURSE) clinical study, the 335 treated patients with metastatic gastric cancer in the placebo-controlled Phase III (TAGS) clinical study, the 246 patients treated with Lonsurf in monotherapy and the 246 patients treated with Lonsurf in combination with bevacizumab for metastatic colorectal cancer in the controlled Phase III (SUNLIGHT) clinical study are shown in Tables 9a and 9b. They are classified according to System Organ Class (SOC) and the appropriate Medical Dictionary for Regulatory (MedDRA) term is used to describe a certain drug reaction and its synonyms and related conditions.
Adverse reactions known to occur with Lonsurf given alone or with bevacizumab may occur during treatment with these medicinal products in combination, even if these reactions were not reported in clinical trials with combination therapy.
Adverse drug reactions are grouped according to their frequencies. Frequency groups are defined by the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); and rare (≥1/10,000 to <1/1,000).
Within each frequency group, adverse drug reactions are presented in order of decreasing seriousness. (See Tables 9a and 9b.)

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Elderly: Patients 65 years of age or older who received Lonsurf as monotherapy had a higher incidence (≥5%) of the following treatment-related adverse events compared to patients younger than 65 years: neutropenia (58.9% vs 48.2%), severe neutropenia (41.3% vs 27.9%), anaemia (36.5% vs 25.2%), severe anaemia (14.1% vs 8.9%), decreased appetite (22.6% vs 17.4%), and thrombocytopenia (21.4% vs 12.1%). When Lonsurf is used in combination with bevacizumab, patients 65 years of age or older had a higher incidence (≥5%) of the following treatment-related adverse events compared to patients younger than 65 years: neutropenia (75.0% vs 65.1%), severe neutropenia (57.0% vs 41.8%), fatigue (39.0% vs 32.2%), thrombocytopenia (28.0% vs 20.5%), and stomatitis (14.0% vs 8.9%).
Infections: In the Phase III placebo-controlled clinical studies, treatment-related infections occurred more frequently in Lonsurf-treated patients (5.8%) compared to those receiving placebo (1.8%).
In the clinical study in combination with bevacizumab, treatment-related infections occurred similarly in patients who received Lonsurf with bevacizumab (2.8%) compared to Lonsurf-treated patients (2.4%).
Proteinuria: In the Phase III placebo-controlled clinical studies, treatment-related proteinuria occurred more frequently in Lonsurf-treated patients (1.8%) compared to those receiving placebo (0.9%), all of which were Grade 1 or 2 in severity (see Precautions).
In the clinical study in combination with bevacizumab, one patient who received Lonsurf with bevacizumab (0.4%) reported a treatment-related proteinuria which was Grade 2 and none among the Lonsurf-treated patients (see Precautions).
Radiotherapy: There was a slightly higher incidence of overall haematological and myelosuppression-related adverse reactions for patients who received prior radiotherapy compared to patients without prior radiotherapy in RECOURSE (54.6% versus 49.2%, respectively), of note febrile neutropenia was higher in Lonsurf-treated patients who received prior radiotherapy vs. those that did not.
In the clinical study in combination with bevacizumab, no increase of incidence of overall haematological and myelosuppression-related adverse reactions was observed for patients who received prior radiotherapy compared to patients without prior radiotherapy in both arms in SUNLIGHT: Lonsurf with bevacizumab (73.7% versus 77.4%) and in Lonsurf-treated patients (64.7% versus 67.7%).
Post-marketing experience in patients with unresectable advanced or recurrent colorectal cancer: There have been reports of interstitial lung disease in patients receiving Lonsurf post approval.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.