2017 was an extremely busy year for the US Food and Drug Administration (FDA) in the field of oncology and hematology. Including new drug approvals, expanded indications, new devices, and diagnostic tests, there were more than 50 approvals in 2017. Immunotherapy once again was the shining star, with a number of new indications for immune checkpoint inhibitors, with indications for pretreated metastatic cancers with high levels of microsatellite instability (MSI-H) and cancers with limited treatment options, such as hepatocellular cancer, Merkel cell carcinoma, and gastric cancer. In addition, the first genetically engineered immunotherapy, chimeric antigen receptor (CAR) T cells, was approved for relapsed/refractory hematologic malignancies, such as acute lymphoblastic lymphoma (ALL) and certain types of non-Hodgkin lymphoma. Several new targeted therapies also became available for different treatment lines in patients with solid tumors and hematologic malignancies. In addition, two biosimilar monoclonal antibodies, copies similar to the originators bevacizumab and trastuzumab, entered the US market, with hopes that they will reduce the cost of these expensive biologics.
To close the year, the FDA issued the following five approvals for anticancer agents and a next-generation comprehensive genomic profiling test.
- Adjuvant Nivolumab for Melanoma. On 20 December 2017, the indication of nivolumab (Opdivo®, Bristol-Myers Squibb) was expanded to include adjuvant treatment after complete resection in patients with high-risk melanoma (lymph node involvement) or after complete resection of metastatic disease. This approval was based on the impressive improvement in recurrence-free survival (RFS) seen with nivolumab in the CheckMate 238 trial. The 12-month rate of RFS was 70.5% for patients treated with nivolumab compared to 60.8% for patients treated with ipilimumab (hazard ratio [HR] 0.65, P<.001). Treatment-related adverse events (AEs) occurred less frequently in patients treated with nivolumab (grade 3/4: 14.4% vs 45.9%). The FDA-recommended dose for adjuvant therapy is 240 mg intravenously (IV) every 2 weeks for a maximum of one year.
- Adjuvant Pertuzumab for HER2-Positive Breast Cancer. Based on results from the large randomized phase III APHINITY trial, the FDA approved pertuzumab (PERJETA®, Genentech) for use in combination with trastuzumab and chemotherapy as adjuvant therapy for patients with high-risk HER2-positive early breast. After a median follow-up of 45.4 months, adjuvant treatment with pertuzumab, trastuzumab, and chemotherapy resulted in an 18% reduction in the risk of developing invasive disease or death (HR 0.82, P = .047). The invasive disease-free survival benefits were more pronounced among patients with higher risk for recurrence. Overall survival data are not yet mature. Diarrhea, anemia, and neutropenia were the most common grade 3 or higher adverse events reported in the trial.
- Cabozantinib Gets Greenlight for First-Line Renal Cell Carcinoma. The indication of the tyrosine kinase inhibitor (TKI) cabozantinib (Cabometyx®, Exelixis) was expanded to include previously untreated patients with advanced renal cell carcinoma (RCC). Cabozantinib has previously been approved for second-line treatment of patients with advanced RCC who have received prior antiangiogenic therapy. Approval in the front-line setting was based on results from the CABOSUN trial, in which cabozantinib significantly improved progression-free survival (assessed by blinded independent radiology review committee) compared to standard of care sunitinib in poor-risk or intermediate-risk patients with RCC (8.6 months vs 5.3 months; HR 0.48, P = .0008). Cabozantinib was also associated with significant improvement in the objective response rate (46% vs 18%). Rates of AEs were similar between the two treatment arms, though the AE profiles differed. Sunitinib was associated with higher rates of hematologic AEs, while cabozantinib was associated with higher rates of gastrointestinal AEs and palmar-plantar erythrodysesthesia syndrome.
- First Trastuzumab Biosimilar Approved in the United States. On 1 December 2017, the FDA approved the first trastuzumab biosimilar (Ogivri®, trastuzumab-dkst, Mylan) in the United States. Ogivri was approved on the basis of extensive comparison to Herceptin® (Genentech), which included analytic studies, human pharmacokinetic and pharmacodynamic comparison, and clinical trials including immunogenicity studies. On the basis of these studies, Ogivri was found to be highly similar to Herceptin with no clinically meaningful differences between the two agents. It has been approved for all the indications of Herceptin, including both breast and gastric cancer. It has been approved as a biosimilar and not an interchangeable product.
- Bosutinib Gains Approval for First-Line Chronic Myelogenous Leukemia Treatment. Bosutinib (Bosulif®, Pfizer), a BCR-ABL TKI initially approved for second-line treatment of Philadelphia chromosome (Ph)‒positive chronic phase (CP) chronic myelogenous leukemia (CML), was granted approval for use in newly diagnosed patients with Ph-positive CP-CML. The expanded indication was based on results from the phase III BFORE trial, in which 47.2% of treatment-naïve patients treated with bosutinib achieved a major molecular response (MMR) at 12 months, compared to 36.9% of patients treated with imatinib (P = .02). Complete cytogenic response (CCyR) rate by 12 months was also significantly higher with bosutinib (77.2 % vs 66.4%, P = .0075). Bosutinib was associated higher rates of grade 3/4 diarrhea (8% vs 1%) and liver toxicity (24% vs 4%) than that found with imatinib.
- First Comprehensive Genomic Profiling Assay Approved. The FDA granted approval for FoundationOne CDx (F1CDx), a next-generation sequencing (NGS) in vitro diagnostic that detects 324 different genetic aberrations and two genomic signatures in any solid tumor type. It also detects microsatellite instability (MSI) and tumor mutation burden. The test can identify which patients with non-small lung cancer (NSCLC), melanoma, breast cancer, colorectal cancer, or ovarian cancer may benefit from currently approved targeted treatment options for these cancers. Clinical performance of the test was established by comparing F1CDx to previously FDA-approved companion diagnostics used to determine patient eligibility for certain treatments. The ability of the test to detect select mutation types of the entire 324 gene panel is accurate approximately 94.6% of the time. Concurrent with this approval, the Centers for Medicare and Medicaid Services (CMS) announced they would provide insurance coverage for FoundationOne CDx.