The FDA ( U.S. Food and Drug Administration ) has granted approval for a new indication for Alimta ( Pemetrexed for injection ) in combination with Pembrolizumab ( Keytruda ) and Platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer ( NSCLC ), with no EGFR or ALK genomic tumor aberrations.
This indication is approved based on data from phase 3 KEYNOTE-189 trial, which enrolled patients regardless of PD-L1 expression and had dual primary endpoints of overall survival ( OS ) and progression-free survival ( PFS ).
Alimta in combination with Pembrolizumab and Carboplatin was first approved in June 2018 under the FDA's accelerated approval process for the first-line treatment of patients with metastatic nonsquamous NSCLC, based on tumor response rates and PFS data from the phase 2 study KEYNOTE-021 ( Cohort G1 ).
In accordance with the accelerated approval process, continued approval was contingent upon verification and description of clinical benefit, which has now been demonstrated in the KEYNOTE-189 trial and has resulted in the FDA converting the accelerated approval to full ( regular ) approval.
KEYNOTE-189 has demonstrated an effect of the Pemetrexed - Pembrolizumab - Platinum chemotherapy combination in the first-line setting, offering significantly improved survival in patients with metastatic nonsquamous non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations.
In the KEYNOTE-189 study, safety was evaluated in 405 patients who received Pemetrexed in combination with Pembrolizumab and Platinum chemotherapy and 202 patients who received placebo, Pemetrexed and Platinum chemotherapy.
Pemetrexed was discontinued for adverse reactions in 23% of patients in the Pemetrexed - Pembrolizumab - Platinum chemotherapy arm. The most common adverse reactions resulting in discontinuation of Pemetrexed in this arm were acute kidney injury ( 3% ) and pneumonitis ( 2% ). Adverse reactions leading to the interruption of Pemetrexed occurred in 49% of patients in the Pemetrexed - Pembrolizumab - Platinum chemotherapy arm; the most common adverse reactions or laboratory abnormalities leading to interruption of Pemetrexed in this arm ( greater than or equal to 2% ) were neutropenia ( 12% ), anemia ( 7% ), asthenia ( 4% ), pneumonia ( 4% ), thrombocytopenia ( 4% ), increased blood creatinine ( 3% ), diarrhea ( 3% ), and fatigue ( 3% ).
Adverse reactions of any grade occurring in greater than or equal to 20% of patients receiving Pemetrexed in combination with Pembrolizumab and Platinum chemotherapy were nausea ( 56% ), fatigue ( 56% ), constipation ( 35% ), diarrhea ( 31% ), decreased appetite ( 28% ), rash ( 25% ), vomiting ( 24% ), cough ( 21% ), dyspnea ( 21% ) and pyrexia ( 20% ). ( Xagena )
Soource: Lilly, 2019