In September, the US Food and Drug Administration (FDA) approved seven new indications in oncology and hematology, including the first ever biosimilar monoclonal antibody (mAb) for the treatment of cancer.
- Bevacizumab Biosimilar Now Available in the United States. On 14 September, the FDA granted approval to bevacizumab-awwb (Mvasi™, Amgen Inc), a biosimilar of Avastin®. This is the first approval of a biosimilar for a cancer treatment. Mvasi™ is approved for several indications of the originator, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), glioblastoma, renal cell carcinoma (RCC), and cervical cancer. The approval was based on demonstration of similarity to Avastin® across all stages of development, including analytic, quality, pharmacokinetic (PK), and efficacy and safety studies. Clinical trials included a PK study comparing Mvasi™ to Avastin® in healthy volunteers and a phase III trial comparing Mvasi™ to Avastin® in patients with advanced NSCLC. Across all stages of development there were no clinically meaningful differences between Mvasi™ and Avastin® in terms of response, safety, purity, and potency. Similar to Avastin®, the label for Mvasi™ will include a boxed warning regarding the increased risk of gastrointestinal (GI) perforations, surgery and wound healing complications, and severe or fatal hemorrhage.
- Nivolumab: First Immunotherapy for Hepatocellular Carcinoma. The FDA granted accelerated approval to the programmed death receptor 1 (PD-1) inhibitor nivolumab (Opdivo®, Brisol-Myers Squibb) for treatment of hepatocellular carcinoma (HCC) in patients who have progressed on sorafenib. Nivolumab (240 mg flat dose every two weeks) is the first immunotherapy to be approved for HCC. The approval was based on results from a 154-patient subgroup of the CheckMate-040 trial, which included patients with HCC and Child-Pugh A cirrhosis who had progressed on or were intolerant to sorafenib. In this study, treatment with nivolumab was associated with an overall response rate (ORR) of 14.3%, including 3 complete responses (CR) and 19 partial responses (PR). Responses were durable, with 91% of responses maintained at 6 months and 55% at 12 months. Adverse events (AEs) were consistent with the known safety profile of nivolumab.
- Pembrolizumab Indication Extended to PD-L1–Positive Gastric Cancer. The PD-1 inhibitor pembrolizumab (Keytruda®, Merck & Co Inc) received accelerated approval for treatment of advanced gastric or gastroesophageal junction adenocarcinoma in patients whose tumors express PD-L1 (combined positive score ≥1) who have progressed on two or more systemic therapies, including fluoropyrimidine and platinum-containing chemotherapy and, if appropriate, HER2-targeted therapy. The recommended pembrolizumab dose for gastric cancer is 200 mg every 3 weeks up to 24 months or until disease progression or unacceptable toxicity. In the , [[https://cslide.ctimeetingtech.com/esmo2017/confcal/LBA28-PR]] pembrolizumab resulted in an ORR of 13.3% and CR rate of 1.4% in patients with PD-L1-positive gastric cancer. The PD-L1 IHC 22C3 pharmDx (Dako), a PD-L1 screening assay, was also approved for use with pembrolizumab in gastric cancer.
- New CDK4/6 Inhibitor for Hormone Receptor–Positive Advanced Breast Cancer. The cyclin-dependent kinase 4/6 (CD 4/6) inhibitor abemaciclib (Verzenio®, Eli Lilly) received approval for treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. It is approved for use in combination with fulvestrant in patients with disease progression following endocrine therapy and as a monotherapy in patients who have progressed on both endocrine therapy and chemotherapy. The approval in combination with fulvestrant was based on results from the phase III MONARCH 2 trial, in which abemaciclib plus fulvestrant significantly improved PFS compared to fulvestrant alone (16.4 months vs 9.3 months; hazard ratio 0.553, P<.001). Approval as a monotherapy was based on the single-arm MONARCH 1 trial, in which treatment with abemaciclib resulted in a mPFS of 6.0 months and median OS of 17.7 months. Abemaciclib is the third CDK 4/6 inhibitor to be approved in advanced breast cancer, following palbociclib and ribociclib; however, it is the only CDK4/6 inhibitor that can be used as monotherapy in heavily pretreated patients.
- Gemtuzumab Ozogamicin Once Again Available in United States for Acute Myeloid Leukemia. Gemtuzumab ozogamicin (Mylotarg™, Pfizer), a CD33-targeting antibody-drug conjugate (ADC), gained approval for treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia (AML) and patients aged 2 years and older with relapsed/refractory CD33-positive AML. This approval was based on combined data from several trials, including the phase III ALFA-0701 trial, the phase III Study AML-19, and the phase II MyloFrance-1 study. In ALFA-0701, gemtuzumab ozogamicin was associated with a 5.9-month improvement in event-free survival (EFS) compared to daunorubicin and cytarabine in adults with newly diagnosed AML. Gemtuzumab ozogamicin was well-tolerated across all studies, including in elderly or frail patients who could not tolerate other AML treatments. It will carry a boxed warning for hepatotoxicity, including veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
- Copanlisib: New Treatment for Relapsed Follicular Lymphoma. The phosphatidylinositol 3-kinase (PI3K)-alpha/delta inhibitor copanlisib (Aliqopa®, Bayer Pharmaceuticals) received accelerated approval for the treatment of patients with relapsed follicular lymphoma who have progressed on at least 2 prior systemic therapies. This approval was based on results from the phase II CHRONOS-1 trial, in which copanlisib treatment resulted in an ORR of 59.2% and a median PFS of 11.2 months in patients with multiple types of lymphoma. The most common all-grade AEs included hyperglycemia, hypertension, and decreased neutrophil count.
- Low-Dose Cabazitaxel Approved in Prostate Cancer. The FDA approved use of the chemotherapy cabazitaxel (Jevtana,®, Sanofi-Aventis) at a reduced dose of 20 mg/m2 in patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with docetaxel. Cabazitaxel was originally approved at a dose of 25 mg/m2. Approval of the reduced dose was based on results from the PROSELICA noninferiority trial in 1200 patients with mCRPC. In this trial, the lower dose of cabazitaxel was associated with a similar median OS compared to the higher dose (13.4 months vs 14.5 months; HR 1.024), but a much more tolerable AE profile. Lower-dose cabazitaxel was associated with fewer deaths, lower rates of grade 3/4 infections, and decreased incidence of febrile neutropenia compared to the higher dose.