Assays Break New Ground in Oncology

Two novel imaging agents and 6 clinical assays for use in cancer care gained the FDA’s approval in 2016, marking advances in the diagnostic field during a relatively slow year for new oncology drugs.

The imaging agents are categorized as new molecular entities (NMEs), which the FDA defines as products that contain a previously unapproved active ingredient either as part of a single drug or in a combination regimen; in some instances, these ingredients may be closely related to agents that have gained prior approvals. Overall, the agency approved 7 NMEs in oncology during 2016.

The novel diagnostics that passed muster for US marketing are both radioactive positron emission tomography (PET) agents. In May, the FDA approved fluciclovine F 18 (Axumin) for PET imaging in men with suspected prostate cancer recurrence based on elevated blood prostate-specific antigen levels following prior treatment. Blue Earth Diagnostics Ltd, the company that developed the product, said it is the first such F 18 imaging agent to gain an indication in that clinical setting.

In June, the FDA approved gallium Ga 68 dotatate (Netspot) for localization of somatostatin receptor—positive neuroendocrine tumors in adult and pediatric patients. Ga 68 dotatate positron-emitting analogue of somatostatin that binds to such receptors, is marketed by Advanced Accelerator Applications USA, Inc.

Vysis CLL FISH Probe Kit

In terms of new assays, the FDA approved following tests in 2016:The Vysis CLL FISH Probe Kit was approved as a companion diagnostic to venetoclax (Venclexta), a BCL-2 inhibitor intended for patients with chronic lymphocytic leukemia (CLL) following at least 1 prior therapy. The kit, which contains 5 reagents sufficient to process 20 assays, also can be used to assess untreated patients.

The test detects deletion of the locus-specific identifier TP53 gene, found on the short arm of chromosome 17p, via fluorescence in situ hybridization (FISH) in peripheral blood specimens from patients with B-cell CLL to identify patients who could be eligible for treatment with venetoclax.

In untreated patients, the assay may be used to dichotomize CLL based on genotype group, and may be used as an aid in determining disease prognosis in combination with additional biomarkers, morphology, and other clinical information. However, the test is not intended for monitoring residual disease.

Ventana PD-L1 (SP142) Assay

The Vysis CLL FISH Probe Kit was approved in April 2016, and is manufactured by Abbott Molecular.The Ventana PD-L1 (SP142) assay, approved as a complementary diagnostic for atezolizumab (Tecentriq), assesses whether patients who have bladder cancer have PD-L1 in their tumor tissue. This will help practitioners treating patients with bladder cancer decide if atezolizumab, a PD-L1 inhibitor, is the best treatment option after platinum-based chemotherapy.

The assay takes a small tissue sample of the patient’s tumor and stains the sample to detect the presence (or absence) of PD-L1-expression. Patients with either a positive or negative test result can benefit from the drug atezolizumab; however, patients whose bladder cancer has high PD-L1 may have greater benefit to atezolizumab than in patients whose bladder cancer does not have PDL1.

cobas EGFR Mutation Test

The Ventana PD-L1 (SP142) assay was approved in May 2016, and is manufactured by Ventana Medical Systems, Inc.The cobas EGFR Mutation Test v2 was approved for use with plasma samples as a companion diagnostic for the non—small cell lung cancer (NSCLC) drug erlotinib (Tarceva). This is the first FDA approval of a liquid biopsy test as an aid in clinical decisions, and makes the cobas EGFR Mutation Test v2 the only FDA-approved test for the detection of the EGFR gene in DNA derived from plasma or tumor tissue.

With this test, the presence of specific NSCLC mutations [exon 19 deletion or exon 21 (L858R) substitution mutations] detected in patients’ blood samples aids in selecting patients who may benefit from treatment with erlotinib. However, if such mutations are not detected in the blood, then a tumor biopsy should be performed to determine if the mutations are present. If the test shows positive results, it may benefit patients who may be too ill or unable to provide a tumor specimen for EGFR testing.

QuantideX qPCR BCR-ABL IS Kit

The cobas EGFR Mutation Test v2 was approved in June 2016, and is manufactured by Roche Molecular Systems.The FDA has given marketing approval to the first nucleic acid—based test for quantifying BCR-ABL1 fusion transcripts as a tool for monitoring patients with chronic myeloid leukemia (CML) who are receiving tyrosine kinase inhibitor therapies directed at the mutation.

The QuantideX qPCR BCR-ABL IS Kit, which uses whole blood specimens, demonstrated a high level of analytical sensitivity in human RNA. The company said the test could detect BRC-ABL1 RNA in ≥95% of patients at MR 4.7 (log molecular reduction from 100% IS).

cobas HPV Test

Although the test detects BCR-ABL fusions, it does not differentiate between e13a2 or e14a2 fusion transcripts and it cannot be used to monitor other rare transcripts, the FDA’s Center for Devices and Radiological Health said. The test also is not intended for the diagnosis of CML. The QuantideX qPCR BCR-ABL IS Kit was approved in July 2016, and is manufactured by Asuragen.The FDA has approved the cobas HPV Test for use with SurePath Preservative Fluid for the detection of human papillomavirus (HPV) in cervical cells obtained for a Pap test, a move that is expected to expand options for processing laboratory samples.

It is the first HPV test approved for use with SurePath Preservative Fluid, 1 of 2 approved liquid collection fluids commonly used for Pap tests. “Many labs have a preference in how samples are collected for processing, and this additional approval gives them another clinically validated option for the cobas HPV test,” said Uwe Oberlaender, head of Roche Molecular Diagnostics.

FoundationFocus CDxBRCA Assay

The test is approved for women age 30 and older in order to determine whether additional follow-up and diagnostic procedures are needed, and for women 21 and older who have already had abnormal Pap test results. It is not approved as a first-line primary HPV screening test. The cobas HPV Test was approved in July 2016, and is manufactured by Roche Molecular Diagnostics.The FoundationFocus CDxBRCA assay was approved for use as a companion diagnostic to aid in identifying women with ovarian cancer for whom treatment with rucaparib (Rubraca) could be beneficial. Rucaparib, a therapy developed by Clovis Oncology, is a PARP inhibitor indicated as a monotherapy for the treatment of patients with deleterious BRCA mutation-associated advanced ovarian cancer who have been previously treated with chemotherapy.

The genomic assay tests tissue samples for BRCA1 and BRCA2 mutations. It may identify more women with ovarian cancer who would benefit from treatment with rucaparib compared with conventional testing methods. The FoundationFocus CDxBRCA assay was approved in December 2016, and is manufactured by Foundation Medicine, Inc.