FDA Approvals for Cancer Management in December 2021
Even as the world continued to struggle through the second year of the COVID-19 pandemic, many effective agents were added to the oncology clinician’s toolbox in 2021. The United States Food and Drug Administration (FDA) once again granted more than 60 new indications to cancer therapies and diagnostic tests. In December alone, four agents for indications in hematology/oncology were approved, including:
- Pembrolizumab for Adjuvant Treatment of Stage IIB or IIC Melanoma. Approval was granted to pembrolizumab (Keytruda®, Merck) for the adjuvant treatment of adult and pediatric (≥12 years of age) patients with stage IIB or IIC melanoma following complete resection. This approval was based on efficacy results from the multicenter, randomized, double-blind, placebo-controlled , in which patients were randomized to receive either pembrolizumab or placebo for up to one year until disease recurrence or unacceptable toxicity. At the first prespecified interim analysis, pembrolizumab treatment resulted in a significant improvement in recurrence-free survival (RFS) compared with placebo, reducing the risk of death or recurrence by 35% (hazard ratio [HR] 0.65). Median RFS was not reached in either arm.
- Another Subcutaneous Daratumumab Combo for Multiple Myeloma. Approval was granted to the subcutaneous formulation of daratumumab + hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc.) in combination with carfilzomib (Kyprolis, Amgen, Inc.) plus dexamethasone (D-Kd regimen) for adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy. This approval was based on efficacy results from a cohort of the single-arm, open-label, multi-cohort phase II PLEIDAS trial. The main efficacy outcome measure was overall response rate (ORR). The ORR for the D-Kd regimen was 84.8% and at median follow up of 9.2 months, the median duration of response had not been reached. An estimated 85.2% of patients maintained response for at least 6 months and 82.5% maintained response for at least 9 months.
- Rituximab Plus Chemotherapy for Pediatric Cancers. Approval was granted to rituximab (Rituxan, Genentech, Inc.) in combination with chemotherapy for pediatric patients (≥6 months to <18 years) with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL). Efficacy results from the open-label, randomized, phase III Inter-B-NHL Ritux 2010 trial that compared the addition of rituximab to standard Lymphomes Malin B (LMB) chemotherapy supported this approval. The main efficacy outcome measure was event-free survival (EFS), reported as a prespecified interim analysis with a median follow-up of 3.1 years. There were 28 EFS events in the standard chemotherapy group and 10 in the rituximab-chemotherapy group (HR 0.32; P=0.0012). Only 8 deaths occurred in the rituximab-chemotherapy group compared to 20 deaths in the chemotherapy-alone arm, with an estimated overall survival HR of 0.36.
- Abatacept Combo to Prevent Acute Graft Versus Host Disease. Abatacept (Orencia, Bristol-Myers Squibb Company), a selective T-cell costimulation modulator, is the first drug to receive approval for prevention of acute graft versus host disease (aGVHD), a serious complication that can develop after allogenic hematopoietic stem cell transplantation (HSCT). Abatacept is approved for use in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX), for adults and pediatric patients at least 2 years of age undergoing HSCT from a matched or 1 allele-mismatched unrelated donor. In addition to real-world data, approval was based on efficacy and safety data of abatacept in combination with a CNI and MTX from two trials in patients aged 6 years and older who underwent allogeneic HSCT, the phase II GVHD-1 trial (also known as ABA2) and GVHD-2, a clinical study using registry data from the Center for International Blood and Marrow Transplant Research. The GVHD-1 trial had 2 cohorts and enrolled patients with fully matched donors (8/8 human leukocyte antigen [HLA]-matched) in placebo-controlled randomized cohort and patients with 1 allele- mismatched, unrelated donors (7/8 HLA-matched) in a single-arm cohort. In both cohorts, efficacy was established based on OS and grade II-IV aGvHD-free survival results assessed at day 180 post-transplantation. While abatacept did not significantly improve severe-aGVHD-free survival in the randomized cohort (HR 0.55), OS was improved (97% vs 84%, HR 0.33) compared to the CNI and MTX-only group. The GVHD-2 study evaluated patients who underwent a 7/8 HLA-matched transplant during a 7-year period. Patients treated with abatacept combination had significantly better OS at day 180 after transplant compared with those who did not receive abatacept (98% vs 75%).