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FDA expands Alimta approval for lung cancer
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The FDA expanded the approval of pemetrexed for injection to include its use in combination with pembrolizumab and platinum chemotherapy for first-line treatment of metastatic nonsquamous non-small cell lung cancer.
The approval applies to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
Pemetrexed for injection (Alimta, Eli Lilly) is a type of chemotherapy indicated for several specific subgroups of patients with NSCLC, as well as initial treatment of patients with malignant pleural mesothelioma who have unresectable disease or are not candidates for curative surgery.
The FDA based the newest indication on results of the randomized, phase 3 KEYNOTE-189 trial, which included 616 untreated patients with metastatic nonsquamous NSCLC regardless of PD-L1 expression. Patients had no ALK or EGFR genomic tumor aberrations and had not received prior systemic therapy for advanced disease.
Researchers randomly assigned 405 patients to pemetrexed plus pembrolizumab (Keytruda, Merck) and either cisplatin or carboplatin. The other 202 patients received pemetrexed plus placebo and either cisplatin or carboplatin.
OS and PFS assessed by blinded independent central review served as primary endpoints. Overall response rate and duration of response serve as secondary endpoints.
Results showed patients assigned the pemetrexed-pembrolizumab regimen achieved significantly longer median PFS (8.8 months vs. 4.9 months; HR – 0.52; 95% CI, 0.43-0.64) and OS (not reached vs. 11.3 months; HR – 0.49; 95% CI, 0.38-0.64).
The most common any-grade adverse reactions that occurred in the pemetrexed-pembrolizumab group were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%) and pyrexia (20%).
Twenty-three percent of patients assigned the pemetrexed-pembrolizumab regimen discontinued treatment due to adverse reactions, the most common of which were kidney injury (3%) and pneumonitis (2%).
Forty-nine percent of patients in this group required treatment interruption due to adverse reactions, the most common of which were neutropenia (12%), anemia (7%), anemia (4%), asthenia (4%), pneumonia (4%) and thrombocytopenia (4%).
In June, the FDA granted accelerated approval to pemetrexed in combination with pembrolizumab and carboplatin for first-line treatment of metastatic nonsquamous NSCLC. The agency based the accelerated approval on tumor response rates and PFS data from the phase 2 KEYNOTE-021 study. Additional data from KEYNOTE-189 prompted the FDA to convert the accelerated approval to full approval.