Balversa Adverse Reactions

The following serious adverse reactions are also described elsewhere in the labeling: Ocular Disorders [see Ocular Disorders under Precautions].
Hyperphosphatemia [see Hyperphosphatemia and Soft Tissue Mineralization under Precautions].
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in the Precautions reflects exposure to BALVERSA as a single agent at the recommended dose (8 to 9 mg orally daily) in 479 patients with advanced urothelial cancer and FGFR alterations in 42756493BLC3001 (NCT03390504), 42756493BLC2001 (NCT02365597), 42756493BLC2002 (NCT 03473743), and 42756493EDI1001 (NCT01703481). Among 479 patients who received BALVERSA, the median duration of treatment was 4.8 months (range: 0.1 to 43 months). In this pooled safety population, the most common (>20%) adverse reactions, including laboratory abnormalities, were increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase, increased alanine aminotransferase, decreased hemoglobin, decreased sodium, increased aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy.
BLC3001: The safety of BALVERSA was evaluated in Cohort 1 of the BLC3001 study that included patients with locally advanced unresectable or metastatic urothelial carcinoma which had susceptible FGFR3 genetic alterations and were previously treated with a PD-1 or PD-L1 inhibitor [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. Patients received either BALVERSA (8 mg orally once daily with individualized up-titration to 9 mg) (n=135) or chemotherapy (docetaxel 75 mg/m² once every 3 weeks or vinflunine 320 mg/m² once every 3 weeks) (n=112). Among patients who received BALVERSA, median duration of treatment was 4.8 months (range: 0.2 to 38 months).
Serious adverse reactions occurred in 41% of patients who received BALVERSA. Serious reactions in >2% of patients included urinary tract infection (4.4%), hematuria (3.7%), hyponatremia (2.2%), and acute kidney injury (2.2%). Fatal adverse reactions occurred in 4.4% of patients who received BALVERSA, including sudden death (1.5%), pneumonia (1.5%), renal failure (0.7%), and cardiorespiratory arrest (0.7%).
Permanent discontinuation of BALVERSA due to an adverse reaction occurred in 14% of patients. Adverse reactions which resulted in permanent discontinuation of BALVERSA in >2% of patients included nail disorders (3%) and eye disorders (2.2%).
Dosage interruptions of BALVERSA due to an adverse reaction occurred in 72% of patients. Adverse reactions which required dosage interruption in >4% of patients included nail disorders (22%), stomatitis (19%), eye disorders (16%), palmar-plantar erythrodysesthesia syndrome (15%), diarrhea (10%), hyperphosphatemia (7%), increased aspartate aminotransferase (6%), and increased alanine aminotransferase (5%).
Dose reductions of BALVERSA due to an adverse reaction occurred in 69% of patients. Adverse reactions which required dose reductions in >4% of patients included nail disorders (27%), stomatitis (19%), eye disorders (17%), palmar-plantar erythrodysesthesia syndrome (12%), diarrhea (7%), dry mouth (4.4%), and hyperphosphatemia (4.4%).
Table 6 presents adverse reactions reported in ≥15% of patients treated with BALVERSA at 8 or 9 mg once daily versus chemotherapy. (See Table 6.)

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Clinically relevant adverse reactions in <15% of patients who received BALVERSA included nausea (15%), pyrexia (15%), epistaxis (13%), vomiting (10%), and arthralgia (10%).
Table 7 presents laboratory abnormalities reported in ≥15% of patients treated with BALVERSA at 8 or 9 mg once daily versus chemotherapy. (See Table 7.)

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BLC2001: The safety of BALVERSA was evaluated in the BLC2001 study that included 87 patients with locally advanced or metastatic urothelial carcinoma which had susceptible FGFR3 and other FGFR alterations, and which progressed during or following at least one line of prior chemotherapy including within 12 months of neoadjuvant or adjuvant chemotherapy [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. Patients were treated with BALVERSA at 8 mg orally once daily; with a dose increase to 9 mg in patients with phosphate levels <5.5 mg/dL on Day 14 of Cycle 1. Median duration of treatment was 5.3 months (range: 0 to 17 months).
Serious adverse reactions occurred in 41% of patients. The most frequent (>3%) serious adverse reactions were central serous retinopathy (4.6%), urinary tract infection (3.4%), and general physical health deterioration (3.4%).
Fatal adverse reactions occurred in 8% of patients, including acute myocardial infarction (1.1%).
Permanent discontinuation of BALVERSA due to an adverse reaction occurred in 21% of patients. The most frequent (≥2%) reasons for permanent discontinuation included central serous retinopathy (4.6%), general physical health deterioration (3.4%), palmar-plantar erythrodysesthesia syndrome (2.3%), acute kidney injury (2.3%), and fatigue (2.3%).
Dosage interruptions of BALVERSA occurred in 68% of patients. The most frequent (≥5%) adverse reactions requiring dosage interruption included hyperphosphatemia (24%), stomatitis (17%), nail disorders (16%), central serous retinopathy (9%), palmar-plantar erythro-dysesthesia syndrome (8%), and fatigue (8%).
Dose reductions of BALVERSA occurred in 53% of patients. The most frequent (≥5%) adverse reactions for dose reductions included nail disorders (21%), stomatitis (15%), central serous retinopathy (14%), hyperphosphatemia (7%), palmar-plantar erythro-dysesthesia syndrome (7%), fatigue (6%), and blurred vision (6%).
Table 8 presents adverse reactions reported in ≥15% of patients treated with BALVERSA at 8 mg or 9 mg once daily. (See Table 8.)

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Clinically relevant adverse reactions in <15% of patients who received BALVERSA included pyrexia (14%), extremity pain (13%), vomiting (13%), and peripheral edema (10%).
Table 9 presents laboratory abnormalities reported in ≥15% of patients treated with BALVERSA at 8 mg or 9 mg once daily. (See Table 9.)

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