New Cancer Drugs and Diagnostics in WHO Essential 2019 Lists

New cancer drugs and cancer diagnostic tests have been added to the World Health Organization's (WHO's) lists of essential medicines and essential diagnostic tests.

"Around the world, more than 150 countries use WHO's essential medicines list to guide decisions about which medicines represent the best value for money, based on evidence and health impact," said WHO Director-General Tedros Adhanom Ghebreyesus, PhD.

"The inclusion in this list of some of the newest and most advanced cancer drugs is a strong statement that everyone deserves access to these lifesaving medicines, not just those who can afford them," he added in a statement.

The new essential medicines list (EML) includes several higher-priced products, such as immunotherapies with checkpoint inhibitors for melanoma and targeted therapies for lung cancer, among others.

Essential Medicines

The WHO defines essential medicines as those that satisfy the priority healthcare needs of the population. The drugs are selected with regard to disease burden, evidence regarding efficacy and safety, and comparative cost-effectiveness.

The WHO Model Lists of Essential Medicines began in 1977. The list for general medicines is updated every 2 years, but updates to the cancer-specific list have been more sporadic. The most substantial reviews of cancer medicines were conducted in 1984, 1994, and 1999. The latest review was conducted in 2015, when 16 new oncologic therapeutics were added.

For this latest review, the expert committee has endorsed the EML Cancer Medicines Working Group's recommendations that the WHO adopt a threshold for benefit of at least 4 to 6 months' survival gain in order for a drug to be considered as a candidate for inclusion in the list.

The committee has acknowledged the ESMO‒Magnitude of Clinical Benefit Scale (ESMO–MCBS) as a screening tool to identify cancer treatments that have potential therapeutic value. It recommended that candidates for inclusion in the EML of cancer medicines generally have a score on the ESMO-MCBS of A or B in the curative setting and of 4 or 5 in the noncurative setting.

The expert committee recommended adding the following new cancer drugs to the EML:

Nivolumab (Opdivo, Bristol-Myers Squibb) for frontline monotherapy for patients with unresectable and metastatic melanoma. (Pembrolizumab [Keytruda, Merck] is listed as a therapeutically equivalent alternative.) This is the first time that the EML has listed therapies for metastatic melanoma.
Bortezomib (Velcade, Millenneium), lenalidomide (Revlimid, Celgene), thalidomide (Thalomid, Celgene), and melphalan (multiple brands) are indicated for patients with newly diagnosed multiple myeloma in both nontransplant and transplant eligible/available settings. These are the first drugs for multiple myeloma to be included on the EML.
Erlotinib (Tarceva, Genentech) is indicated for frontline treatment of EGFR mutation–positive advanced non–small cell lung cancer (with afatinib [Gilotrif, Boehringer Ingelheim Pharmaceuticals] and gefitinib [Iressa, AstraZeneca Pharmaceuticals LP] listed as therapeutically equivalent alternatives).
Abiraterone (Zytiga, Janssen) is indicated for patients with metastatic castration-resistant prostate cancer. (Enzalutamide [Xtandi, Astellas] was not listed.)
Arsenic (Trisenox, Cephalon) (oral and IV formulations) is listed for patients with acute promyelocytic leukemia. (Arsenic is also listed on the EML for children's medicines [EMLc]).
Pegaspargase (Oncaspar, Sigma Tau) was recommended for the treatment of patients with acute lymphoblastic leukemia.

For several of the cancer therapies currently on the EML, it was recommended that indications be extended to include cervical cancer and multiple myeloma. In addition, it was recommended that indications for 10 medicines currently on the EML be extended to the EMLc. Indications were extended for 11 agents currently included on the EMLc.

The expert committee also considered several newer cancer therapies but decided not to recommend them for inclusion in the EML. Among those rejected were the following:

Nivolumab, pembrolizumab, and atezolizumab (Tecentriq, Genentech) for the treatment of non–small cell lung cancer. The committee considered that their place in therapy for this condition is still evolving and that more data with longer follow-up are needed to better estimate the magnitude of benefit.
Pertuzumab (Perjeta, Genentech/Roche) for HER2-positive breast cancer. The evidence did not demonstrate a clinically meaningful survival benefit in early-stage disease. A large overall survival benefit has been demonstrated in a single trial in metastatic disease, but similar results have not been seen in other trials. The committee recommended that further independent analysis of data from existing and ongoing trials be undertaken to inform future consideration for inclusion in the EML.
Trastuzumab emtansine (Kadcyla, Roche) for HER2-positive breast cancer. Although it yields a survival benefit, its use as second-line treatment of metastatic disease was considered not to be a priority for the treatment of breast cancer. Alternative drugs are listed on the EML.
Subcutaneous formulations of rituximab (Truxima, Celltrion) and trastuzumab (multiple brands). The committee was concerned that listing these medications, for which biosimilars are not yet available, could limit competition and, consequently, access for patients.

Essential (in Vitro) Diagnostics

The first WHO list of essential diagnostics, published last year, included tests to diagnose the most common conditions as well as a limited number of global priority diseases, such as HIV, malaria, tuberculosis, and hepatitis. This year's list was expanded to include more noncommunicable and communicable diseases.

"The list of essential diagnostics was introduced in 2018 to guide the supply of tests and improve treatment outcomes," said Mariângela Simão, MD, WHO assistant director-general for medicines and health products, in a release. "As countries move towards universal health coverage and medicines become more available, it will be crucial to have the right diagnostic tools to ensure appropriate treatment."

Newly added to the 2019 diagnostics list are 12 tests that are used to detect a wide range of solid tumors, including colorectal, liver, cervical, prostate, breast, and germ cell cancers, as well as leukemia and lymphomas.

These diagnostic tests for cancer include the following:

Lactate dehydrogenase activity test, which is used to aid in the prognosis and monitoring of hematologic malignancies (lymphoma) and germ cell tumors.
Estrogen and progesterone receptor tests, used in the diagnosis, prognosis, and treatment of breast cancer.
Tyrosine protein kinase receptor or human epidermal growth factor receptor 2 (HER2) overexpression tests, used in the diagnosis, prognosis, and treatment of breast cancer.
Papanicolaou test, used for cervical cancer screening.
Prostate-specific antigen test, used to aid in diagnosing and monitoring prostate cancer.
Fecal immunochemical test, used for colorectal cancer screening.
Human chorionic gonadotrophin (hCG) plus betahCG, used for the diagnosis and surveillance of germ cell tumors and gestational trophoblastic disease.
Alphafetoprotein immunoassay, used in conjunction with ultrasound for screening for hepatocellular carcinoma in high-risk individuals with liver cirrhosis and those who have a family history. It is also used for the staging and monitoring of germ cell tumors.
Basic panel for immunohistochemical testing, used for the diagnosis of lymphoma, as well as for subclassification, prognosis, and treatment.
Basic panel of immunohistochemical markers, used for the diagnosis of solid tumors.
BCR-ABL1 and ABL1 transcript tests, used for diagnosing and monitoring chronic myelocytic leukemia (CML) and CML variants (neutrophilic CML) and for the prognosis of patients with acute lymphoblastic leukemia.
Essential flow cytometry panel of antibodies for leukemia, used to aid in diagnosing acute leukemias.

Overall, the updated Model List of Essential in Vitro Diagnostics contains 46 general tests and 69 tests intended for the detection, diagnosis, and monitoring of specific diseases. The list is divided into two sections, one for tests to be performed in community settings (including self-testing), and one for tests performed in clinical laboratories.

WHO. Exective Summary, Full text; Second WHO Model List of Essential in Vitro Diagnostics, Full text

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