FDA Drug Approvals: Oncology and Hematology — Year in Review 2018

Mary L Windle, PharmD


January 15, 2019

Other New Oncology Drugs

Vitrakvi (larotrectinib)

Larotrectinib is a tyrosine kinase (TRK) inhibitor that is indicated for adults and children with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or for which surgical resection is likely to result in severe morbidity, and have no alternative treatments or have progressed following treatment.

Chromosomal fusion of TRK has been identified among a wide variety of solid tumors that occur in adults and children. TRK fusions have been shown to activate chimeric proteins, which act as an oncogenic driver by promoting cell proliferation and survival in tumor cell lines.

Approval of larotrectinib was based on clinical trial results of 55 patients aged 4 months to 76 years. Seventeen unique TRK fusion–positive tumor types were represented across the study. The overall response rate was 75% according to independent review and 80% according to investigator assessment. At 1 year, 71% of the responses were ongoing and 55% of the patients remained progression free. (N Engl J Med. 2018 Feb 22;378:731-739)

Libtayo (cemiplimab)

Cemiplimab is a monoclonal antibody that targets checkpoint inhibitor programmed death 1 (PD-1) and blocks its interaction with programmed death ligand-1 (PD-L1) and PD-L2, thereby releasing PD-1 pathway–mediated inhibition of the immune response, including antitumor immune response, and decreasing tumor growth. It is indicated for patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation.

In the metastatic-disease cohort of the EMPOWER-CSCC-1 phase 2 study, a response was observed in 28 (47%) of 59 patients (95% CI, 34-61) who received cemiplimab. The median follow-up was 7.9 months. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. (N Engl J Med. 2018 Jul 26;379(4):341-351)

Talzenna (talazoparib)

Talazoparib is a poly ADP ribose polymerase (PARP) inhibitor. It is indicated for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer.

Approval was based on the phase 3 EMBRACA trial (n=431), in which talazoparib reduced the risk of disease progression or death by 46% compared with physician’s choice chemotherapy (PCT), which included eribulin, gemcitabine, vinorelbine, and/or capecitabine. The overall response rate was 62.6% in the talazoparib group and 27.2% in the PCT group (P<.001). The clinical benefit rate at 24 weeks was 68.6% in the talazoparib group and 36.1% in the PCT group. Overall survival data were not yet mature at publication; however, an interim overall survival analysis found a positive trend favoring talazoparib. The median overall survival was 22.3 months with the PARP inhibitor compared with 19.5 months with chemotherapy. (N Engl J Med. 2018 Aug 23;379(8):753-763)

Erleada (apalutamide)

Apalutamide is an androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. It inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription. It is indicated for nonmetastatic, castration-resistant prostate cancer (NM-CRPC).

Data from the phase 3 SPARTAN (Selective Prostate Androgen Receptor Targeting with ARN-509) trial was the basis for approval. Investigators randomly assigned 806 men to receive treatment with apalutamide (240 mg/day) and 401 to receive placebo; all participants also received hormone therapy, either gonadotropin-releasing hormone analogue therapy or surgical castration.

All of the men had also undergone previous definitive treatment, either surgery or radiotherapy, for prostate cancer, but their prostate-specific antigen scores doubled within 10 months or less following treatment, despite hormone therapy.

Median metastasis-free survival, which was the primary endpoint, was 40.5 months in the apalutamide group compared with 16.2 months in the placebo group (P<.001). That translated to a 72% reduction in the relative risk for metastasis or death with the new drug (hazard ratio, 0.28; 95% CI, 0.23-0.35). (N Engl J Med. 2018 Apr 12;378(15):1408-1418)

Lutathera (lutetium Lu 177-dota-tate)

Lutetium Lu 177-dota-tate is a peptide receptor radionuclide therapy. It binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2). Upon binding to somatostatin receptor–expressing cells, including malignant somatostatin receptor–positive tumors, the compound is internalized. Beta emission from 177Lu induces cellular damage by forming free radicals in somatostatin receptor–positive cells and in neighboring cells. It is indicated for somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Approval of lutetium 177Lu was based on results from the NETTER-1 clinical trial. The trial was a single-institution, single-arm, open-label trial conducted by Erasmus Medical Center in Rotterdam, Netherlands, in more than 1200 patients with somatostatin receptor–positive tumors. Results showed a 79% reduction in risk of disease progression or death in the 177Lu arm compared with octreotide LAR 60-mg arm (95% CI, 0.13-0.32; P<.0001). Median progression-free survival was not reached in the 177Lu arm, compared with 8.5 months for octreotide LAR. An interim overall survival analysis determined that 177Lu treatment led to a 48% reduction in the estimated risk of death (hazard ratio, 0.52; 95% CI, 0.32-0.84) compared with octreotide LAR. (N Engl J Med. 2017 Jan 12;376(2):125-135)

Akynzeo (netupitant/palonosetron)

Netupitant/palonosetron is a combination antiemetic agent that combines netupitant, a tachykinin neurokinin 1 (NK1) receptor antagonist, plus palonosetron, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The oral capsules are indicated in combination with dexamethasone in adults for prevention of acute and delayed chemotherapy-induced nausea and/or vomiting (CINV), including, but not limited to, highly emetogenic chemotherapy. The intravenous infusion is indicated only for highly emetogenic chemotherapy.

Netupitant/palonosetron was tested in a clinical trial of 1286 participants totaling 5969 chemotherapy cycles. Efficacy of a single oral capsule plus dexamethasone given before anthracycline-cyclophosphamide (AC) and non-AC highly emetogenic chemotherapy showed superior prevention of CINV compared with palonosetron plus dexamethasone (P Support Care Cancer. 2017 Apr;25(4):1127-1135)

An intravenous formulation was also shown effective and was well tolerated. (Ann Oncol. 2018 Jul 1;29(7):1535-1540)


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