Lytgobi

Lytgobi therapy should be initiated by a physician experienced in the diagnosis and treatment of patients with biliary tract cancer. Presence of FGFR2 gene fusions or rearrangements should be confirmed by an appropriate diagnostic test prior to initiation of Lytgobi therapy.

Posology The recommended starting dose is 20 mg futibatinib taken orally once daily. If a dose of futibatinib is missed by more than 12 hours or vomiting occurs after taking a dose, an additional dose should not be taken, and treatment should be resumed with the next scheduled dose.

Treatment should be continued until disease progression or unacceptable toxicity. In all patients, dietary restrictions that limit phosphate intake are recommended as part of hyperphosphatemia management. 5 mg/dL. If the serum phosphate level is > 7 mg/dL, the dose of futibatinib should be modified based on the duration and severity of hyperphosphatemia (see Table 2).

4). If Lytgobi treatment is stopped or serum phosphate level falls below normal range, phosphate-lowering therapy and diet should be discontinued. Severe hypophosphatemia may present with confusion, seizures, focal neurologic findings, heart failure, respiratory failure, muscle weakness, rhabdomyolysis, and hemolytic anemia.

5). If this is not possible, based on careful monitoring of tolerability, a futibatinib dose reduction to the next lower level should be considered. 5). If this is not possible, gradually increasing the futibatinib dose based on careful monitoring of tolerability should be considered.

Management of toxicities Dose modifications or interruption of dosing should be considered for the management of toxicities. The recommended dose reduction levels are provided in Table 1.

Table 1:

Recommended futibatinib dose reduction levels Dose Dose reduction levels 20 mg taken orally once daily First Second 16 mg taken orally once daily 12 mg taken orally once daily Treatment should be permanently discontinued if patient is unable to tolerate 12 mg futibatinib once daily.

Dose modifications for hyperphosphatemia are provided in Table 2. 0 mg/dL within 2 weeks following 2 dose reductions 4 Dose modifications for serous retinal detachment are provided in Table 3.

0%). 4%). 4%),all other adverse reactions were single occurrence. Tabulated list of adverse reactions Table 5 summarises the adverse reactions occurring in 145 patients treated in the indicated population of Study TAS-120-101. 7). Adverse reactions are listed according to MedDRA system organ class (SOC).

Frequency categories are very common (≥ 1/10) and common (≥ 1/100 to < 1/10). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 5:

Adverse reactions observed in the indicated population in TAS-120-101 study (N=145) – frequency reported by incidence of treatment emergent events System organ class Frequency Adverse reactions Metabolism and nutrition disorders Very common Hyperphosphatemia Decreased appetite Hyponatraemia Hypophosphataemia Nervous system disorders Very common Dysgeusia Common Migraine Eye disorders Very common Dry eye Common Serous retinal detachmenta Gastrointestinal disorders Very common Stomatitis Diarrhoea Nausea Constipation Dry mouth Vomiting Abdominal pain Common Intestinal obstruction Skin and subcutaneous tissue disorders Very common Palmar-plantar erythrodysaesthesia syndrome Nail disordersb Dry skin Alopecia Musculoskeletal and connective tissue disorders Very common Myalgia Arthralgia General disorders and administration site conditions Very common Fatigue Investigations Very common Liver transaminases increased a Includes serous retinal detachment, detachment of retinal pigment epithelium, subretinal fluid, chorioretinopathy, macular oedema, and maculopathy.

See below “Serous retinal detachment”. 6% patients had Grade 3 events, defined as serum phosphate > 7 mg/dL and ≤ 10 mg/dL irrespective of clinical symptoms. 0 days). None of the reactions were Grade 4 or 5 in severity, serious, or led to discontinuation of futibatinib.

4. Moderate decrease in visual acuity (best corrected visual acuity 20/40 or better or ≤ 3 lines of decreased vision from baseline); limiting instrumental activities of daily living • Withhold futibatinib. If improved on subsequent examination, futibatinib should be resumed at the next lower dose level.

• If symptoms recur, persist or examination does not improve, permanent discontinuation of futibatinib should be considered based on clinical status. Marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or >3 lines decreased vision from baseline up to 20/200); limiting activities of daily living • Withhold futibatinib until resolution.

If improved on subsequent examination, futibatinib may be resumed at 2 dose levels lower. • If symptoms recur, persist or examination does not improve, permanent discontinuation of futibatinib should be considered based on clinical status.

Visual acuity worse than 20/200 in affected eye; limiting activities of daily living • Permanent discontinuation of futibatinib should be considered based on clinical status. Dose modifications for other adverse reactions are provided in Table 4.

Table 4:

Dose modifications for other adverse reactions Other Adverse Reactions Grade 3a • Withhold futibatinib until toxicity resolves to Grade 1 or baseline, then resume futibatinib – for hematological toxicities resolving within 1 week, at the dose prior to suspending.

– for other adverse reactions, at next lower dose. 03). 1). Renal impairment Dose adjustment is not required for patients with mild and moderate renal impairment (creatinine clearance [CLcr] 30 to 89 mL/min estimated by Cockcroft-Gault).

2). Hepatic impairment No dose adjustment is required when administering futibatinib to patients with mild (Child-Pugh class A), moderate (Child-Pugh class B), or severe (Child-Pugh class C) hepatic impairment. However, there is no safety data in patients with severe hepatic impairment.

1.