fda-approvals-june-2019

New FDA Cancer Indications Approved in March and April

  • Atezolizumab Becomes First Immunotherapy Approved for Breast Cancer. The United States Food and Drug Administration (FDA) granted accelerated approval to the combination of the PD-L1 inhibitor atezolizumab (Tecentriq®, Genentech) and nab-paclitaxel for treatment of patients with PD-L1-positive (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥1% of the tumor area) advanced triple-negative breast cancer (TNBC). This decision was based on results from the phase III IMpassion130 trial, in which atezolizumab plus nab-paclitaxel resulted in a significant improvement in median progression-free survival (PFS) compared to nab-paclitaxel alone (7.5 months vs 5.0 months; HR 0.60, P<.0001) in PD-L1-positive patients with advanced TNBC. Median overall survival (OS) was also improved in PD-L1-positive patients treated with atezolizumab plus nab-paclitaxel (25.0 months vs 15.5 months; HR 0.62). The VENTANA PD-L1 (SP142) Assay was approved as a companion diagnostic alongside atezolizumab.
  • Atezolizumab Included in the First-Line Treatment of Extensive-Stage Small Cell Lung Cancer. Atezolizumab was also granted approval for use in combination with carboplatin and etoposide for first-line treatment of extensive-stage small cell lung cancer (SCLC). In the IMpower133 trial, the addition of atezolizumab to chemotherapy resulted in significant improvements in overall survival (OS) compared to chemotherapy alone (12.3 months vs 10.3 months; HR 0.70, P = .007).
  • Pembrolizumab Monotherapy Indication for NSCLC in First-Line Therapy Expanded to Patients With PD-L1 expression ≥1%. The PD-1 inhibitor pembrolizumab (Keytruda®, Merck) was approved for use as first-line therapy in patients with PD-L1-positive (TPS ³1%, determined by IHC 22C3 pharmDx Kit) locally advanced and metastatic non-small cell lung cancer (NSCLC) whose tumors do not express EGFR or ALK This approval was granted on the basis of results from the Keynote-042 trial, which compared pembrolizumab monotherapy to carboplatin plus either pemetrexed or paclitaxel in patients with previously untreated locally advanced or metastatic NSCLC. Overall survival (OS) in the TPS ≥50% NSCLC subgroup, the TPS ≥20% NSCLC subgroup, and the overall population (TPS ≥1%) were the major efficacy measures. First-line pembrolizumab in TPS ≥1% population (overall population) resulted in a significant improvement in OS, from 12.1 months with chemotherapy alone to 16.7 months with pembrolizumab (HR 0.81, P = .0036). However, the survival benefit was much more pronounced in patients with TPS ≥50% (20 months with pembrolizumab versus 12.2 with chemotherapy; HR 0.69; P = .0006). Pembrolizumab monotherapy was previously approved for first-line treatment of  advanced NSCLC with PD-L1 expression (TPS ≥50%) based on results of KEYNOTE-024 trial.
  • Combination Pembrolizumab and Axitinib for First-line RCC. The FDA also approved the combination of pembrolizumab and axitinib for first-line treatment of patients with advanced renal cell carcinoma (RCC). This decision followed results from the Keynote-426 trial, in which pembrolizumab plus axitinib resulted in a significant improvement in PFS, OS, and ORR compared to sunitinib. While median OS has not yet been reached (HR 0.53, P<.0001), the 12-month OS rate was 90% and 78% in the pembrolizumab plus axitinib and sunitinib arms, respectively. Importantly, unlike the combination of nivolumab and ipilimumab in RCC, which is only approved for intermediate- or poor-risk patients, pembrolizumab plus axitinib is approved for first-line treatment of all patients, regardless of risk status. The benefit of pembrolizumab plus axitinib was observed across all risk groups and regardless of PD-L1 expression status. Overall frequency of adverse events was similar between the two treatment groups, though 20% of patients receiving pembrolizumab plus axitinib had grade 3/4 elevation of liver transaminases.
  • Erdafitinib Approved for FGFR2/3 Mutated Bladder Cancer. Erdafitinib (Balversa®, Janssen), a pan-FGFR inhibitor, received accelerated approval for treatment of patients with advanced urothelial cancer whose tumors carry certain alterations in FGFR 2 or 3 and who have progressed during or following platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant chemotherapy. This approval was based on a cohort of patients with progressive advanced urothelial cancer enrolled on Study BLC2001. Treatment with erdafitinib resulted in an objective response rate (ORR) of 32.2%, including complete responses in 2.3% of patients. Erdafitinib treatment is sometimes associated with ocular disorders (central serous retinopathy or retinal pigment epithelial detachment) and 25% of patients in this cohort experienced visual field defect due to erdafitinib-associated adverse events (AEs). The therascreen® FGFR RGQ RT-PCR Kit was approved for use as a companion diagnostic with erdafitinib.

FDA-Approvals-March-April-2019

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