Drugs Xagena
The Food and Drug Administration ( FDA ) has approved Tremelimumab ( Imjudo ) in combination with Durvalumab ( Imfinzi ) and Platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer ( NSCLC ) with no sensitizing epidermal growth factor receptor ( EGFR ) mutation or anaplastic lymphoma kinase ( ALK ) genomic tumor aberrations.
Efficacy was evaluated in POSEIDON, a randomized ( 1:1:1 ), multicenter, active-controlled, open-label study in patients with metastatic non-small cell lung cancer who had not received prior systemic treatment. Patients were randomized to one of three treatment arms: (1) Tremelimumab, Durvalumab, and Platinum-based chemotherapy for 4 cycles, followed by Durvalumab and maintenance chemotherapy every 4 weeks. Patients were treated with a fifth Tremelimumab dose at week 16; (2) Durvalumab plus Platinum-based chemotherapy for 4 cycles followed by Durvalumab and maintenance chemotherapy; or (3) Platinum-based chemotherapy for 6 cycles followed by maintenance chemotherapy.
Treatment was continued until disease progression or unacceptable toxicity.
This approval is based on a comparison of treatment arm 1 and 3 ( 675 patients ).
The major efficacy outcome measures were progression-free survival ( PFS ) assessed using blinded independent central review according to RECIST v1.1. and overall survival ( OS ).
Tremelimumab plus Durvalumab and Platinum-based chemotherapy has demonstrated a statistically significant and clinically meaningful improvement in overall survival compared to Platinum-based chemotherapy ( hazard ratio [ HR ] of 0.77 [ 95% CI: 0.65, 0.92 ], 2-sided p-value = 0.00304 ); median overall survival was 14 months ( 95% CI: 11.7, 16.1 ) and 11.7 months ( 95% CI: 10.5, 13.1 ) in the treatment arm 1 and 3, respectively.
Median progression-free survival was 6.2 months ( 95% CI: 5.0, 6.5 ) and 4.8 months ( 95% CI 4.6, 5.8 ) in the treatment arms, respectively ( HR 0.72 [ 95% CI: 0.60, 0.86 ], 2-sided p-value = 0.00031 ).
Overall response rate was 39% ( 95% CI: 34,44 ) and 24% ( 95% CI: 20, 29 ) in the treatment arm 1 and 3, respectively.
Median duration of response was 9.5 months ( 95% CI: 7.2, not-reached ) and 5.1 months ( 95% CI: 4.4, 6.0 ) in the two treatment arms.
The most common adverse reactions ( occurring in greater than or equal to 20% of patients ) were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea.
Grade 3 or 4 laboratory abnormalities ( 10% or more ) were neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia, and thrombocytopenia.
The recommended Tremelimumab dose for patients weighing 30 kg or more is 75 mg IV every 3 weeks with Durvalumab 1500 mg IV and Platinum-based chemotherapy for 4 cycles, then Durvalumab 1500 mg with maintenance chemotherapy every 4 weeks. A fifth Tremelimumab dose ( 75 mg ) should be given at week 16.
For patients weighing 30 kg or less, the recommended Tremelimumab dose is 1 mg/kg and the Durvalumab dose is 20 mg/kg. ( Xagena )
Source: FDA, 2022
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