Despite the fact that 2020 will be remembered for the COVID-19 pandemic and the many deaths caused by this devastating disease, last year saw the rapid development of treatments to manage the disease, as well as a considerable increase in therapeutic options for cancer. In 2020, the US Food and Drug Administration (FDA) granted over 60 new indications to cancer therapies and diagnostic tests. In November and December alone, seven cancer therapies and one liquid biopsy next-generation sequencing (NGS) companion diagnostic test have been approved, including:

Margetuximab, for Patients With Pretreated HER2-Positive Breast Cancer.

Margetuximab-cmkb (Margenza™, MacroGenics), a novel immune-enhancing monoclonal HER2-targeted antibody, was approved in combination with chemotherapy for patients with metastatic HER2-positive breast cancer, who have received two or more previous anti-HER2 regimens, with at least one treatment for metastatic disease. The approval was based on results from the randomized phase III SOPHIA trial (n=536) in which margetuximab plus chemotherapy showed a significant 24% reduction in the risk of disease progression, compared with trastuzumab plus chemotherapy, in heavily pretreated HER2-positive breast cancer patients (median PFS: 5.8 versus 4.9 months; hazard ratio [HR], 0.76; P=0.033). The prescribing information includes a boxed warning of the risks of left ventricular dysfunction and embryo-fetal toxicity.

Pembrolizumab for Advanced Triple-Negative Breast Cancer Patients.

Accelerated approval was granted to pembrolizumab (Keytruda®, Merck & Co., Inc.) in combination with chemotherapy, for the treatment of patients with locally recurrent, unresectable, or metastatic triple-negative breast cancer (mTNBC) whose tumors express PD-L1 (combined positive score [CPS] ≥10), as determined by the FDA’s simultaneously approved test for selecting patients with TNBC for pembrolizumab treatment, the PD-L1 IHC ₂₂C₃ pharmDx (Dako North America, Inc.). Approval was based on the results from the double-blind, randomized, placebo-controlled KEYNOTE-355 trial. Median PFS was 9.7 months for patients in the pembrolizumab arm versus 5.6 months in the placebo arm (HR, 0.65; P=0.0012).

Relugolix, a Novel Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist, for Advanced Prostate Cancer.

Approval was granted to the first and only oral GnRH receptor antagonist, relugolix (Orgovyx™, Myovant Sciences, Inc.) for the treatment of patients with advanced prostate cancer, based on efficacy results from the pivotal, open-label, phase III HERO trial (n=930). In this trial, relugolix achieved a rapid and sustained suppression of testosterone to castrate levels (<50 ng/dL through 48 weeks) in 96.7% of men compared with 88.8% of men treated with leuprolide (P<0.001 for superiority). Notably, there was a 54% lower risk of major adverse cardiovascular events in the relugolix arm (HR, 0.46). The recommended relugolix dose is a loading dose of 360 mg on the first day followed by a daily dose of 120 mg.

Osimertinib for Early-Stage EGFR-Mutation-Positive NSCLC.

Third-generation EGFR inhibitor, osimertinib (Tagrisso®, AstraZeneca Pharmaceuticals LP) was approved as adjuvant therapy after tumor resection in patients with NSCLC, whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by the FDA-approved test. The approval was based on results from the randomized, double-blind, placebo-controlled, phase III ADAURA trial (n=682). In patients with resected stage II–III NSCLC, adjuvant osimertinib (80 mg daily for 3 years) yielded significantly longer median disease-free survival (DFS) than placebo (not reached versus 19.6 months; HR, 0.17; P<0.0001). In the overall study population, median DFS was not reached versus 27.5 months, respectively (HR, 0.20; P<0.0001).

Pralsetinib, a New Option for Advanced RET-Altered Thyroid Cancers. Accelerated approval was granted for the highly potent selective RET kinase inhibitor, pralsetinib (Gavreto™, Blueprint Medicines Corp.), for the treatment of patients (≥12 years old) with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine (RAI)-refractory, if appropriate. Results from the open-label, multi-cohort, first-in-human, phase I/II ARROW trial that included patients with RET-altered solid tumors, including thyroid cancer, supported this approval. The MTC cohort achieved an overall response rate (ORR) of 60% in patients previously treated with cabozantinib or vandetinib, and an ORR of 74% in the treatment-naïve patients. Median DOR in both groups of patients was not reached. Among patients with RET fusion-positive thyroid cancer, the ORR was 91% and all responses were durable.

Expanded Indication for Selinexor in Relapsed/Refractory Multiple Myeloma.

A selective inhibitor of nuclear export, selinexor (Xpovio®, Karyopharm Therapeutics Inc.) was approved in combination with bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma, who have received at least one prior therapy. The approval was based on results from the randomized open-label, multicenter, phase III BOSTON trial (n=402) in which once-weekly selinexor orally, in combination with once-weekly bortezomib subcutaneously, and low-dose dexamethasone twice-weekly orally (SVd) demonstrated a substantial, clinically significant improvement in PFS compared with the standard twice-weekly bortezomib plus low-dose dexamethasone (Vd). Median PFS was 13.9 months for the SVd arm versus 9.5 months for the Vd arm (HR, 0.7; P=0.0075).

Naxitamab for Relapsed/Refractory Neuroblastoma in Bone or Bone Marrow.

Accelerated approval was granted to a monoclonal antibody targeting GD2, naxitamab-gqgk (Danyelza®, Y-mAbs Therapeutics, Inc.) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for pediatric (≥1 year old) and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow, who have demonstrated a partial or minor response, or stable disease, to prior treatment. The approval was based on ORR data from two single-arm, open-label, phase II studies: Study 201 and Study 12-230. Among 22 patients treated in Study 201, the ORR was 45%, and 30% of responders had a DOR of ≥6 months. For the 38 patients treated in Study 12-230, the ORR was 34%, and 23% of patients had a DOR of ≥6 months. Responses were observed in either bone or bone marrow in both trials. The prescribing information includes a boxed warning of the risk of serious infusion-related reactions and neurotoxicity.

Liquid Biopsy NGS-Based Companion Diagnostic Test.

Approval was granted for the liquid biopsy NGS-based FoundationOne Liquid CDx test (Foundation Medicine, Inc.) as a companion diagnostic device to identify mutations in BRCA1, BRCA2 and ATM genes in patients with metastatic castration-resistant prostate cancer, who are eligible for treatment with olaparib (Lynparza®, AstraZeneca Pharmaceuticals LP). Previously, the companion diagnostic test was approved for identifying mutations inBRCA1 and BRCA2 genes in patients with ovarian cancer eligible for treatment with rucaparib (Rubraca®, Clovis Oncology, Inc.), to identify ALK rearrangements in patients with NSCLC eligible for treatment with alectinib (Alecensa®, Genentech USA, Inc.), and to identify mutations in the PIK3CA gene in patients with breast cancer eligible for treatment with alpelisib (Piqray®, Novartis Pharmaceutical Corp.).