The U.S. saw a reduction in cancer deaths from 1991 to 2014. According to the latest data from the 2017 Cancer Progress Report, just released by the American Association of Cancer Research (AACR), over 2.1 million lives have been saved.
The AACR cites immunotherapy and precision medicine are at the forefront of this progress. Its 2017 report states that advances in biology, chemistry, physics, and technology have set the stage for the new era of precision medicine.
The report spans 12 months from August 1, 2016, to July 31, 2017.
During that time, the FDA approved seven new molecularly targeted anticancer therapeutics and two new checkpoint inhibitors. In addition, new uses for four previously approved molecularly targeted anticancer therapeutics, dabrafenib (Tafinlar), ibrutinib (Imbruvica), regorafenib (Stivarga), and trametinib (Mekinist), have been approved as well as a first-time approval for treatment based on a tumor’s biomarkers rather than originating location.
Here are the highlights of the nine newly approved cancer drugs—two checkpoint inhibitors and seven molecularly targeted therapeutics—starting with an historic first for a previously approved drug.
Among the biggest news in cancer this year? The FDA approval of pembrolizumab (Keytruda) for any solid tumor with a specific genetic feature. This is the first time the agency had approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated. The drug works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, pembrolizumab may help the body’s immune system fight the cancer cells.
The FDA previously approved Keytruda for the treatment of certain patients with metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.
In March 2017, one of the new checkpoint inhibitors, avelumab (Bavencio), which targets PD-L1, preventing it from attaching to PD-1 and triggering its brake function, was approved for patients with a rare, aggressive form of cancer called Merkel cell carcinoma. The accelerated approval was based on the fact that treatment with avelumab led to tumor shrinkage in about 30 percent of patients enrolled in a phase II clinical trial.
The second new checkpoint inhibitor to be approved by the FDA mentioned by this report is durvalumab (Imfinzi), which also targets PD-L1. Accelerated approval was granted for treating certain patients with the most common form of bladder cancer, urothelial carcinoma, in May 2017. Specifically, it was approved for treating patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed despite treatment with a platinum-based cytotoxic chemotherapeutic.
The decision was based on the fact that treatment with durvalumab led to tumor shrinkage in about 16 percent of patients enrolled in a phase II clinical trial.
Midostaurin (Rydapt) is the first molecularly targeted therapeutic approved for treating AML. It targets several related molecules called tyrosine kinase receptors, including FLT3 and KIT, and was approved in April 2017 for treating adults newly diagnosed with AML harboring a mutation in the FLT3 gene, as detected by an FDA-approved test, or companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay, to identify patients with AML with the FLT3 mutation.
In April 2017, the FDA also approved midostaurin for adult patients with certain aggressive forms of a rare disorder known as systemic mastocytosis. In patients with this disorder, immune cells called mast cells accumulate in internal organs such as the liver, spleen, bone marrow, and small intestines.
In October 2016, the FDA granted accelerated approval to the molecularly targeted therapeutic olaratumab (Lartruvo) for treating patients with soft tissue sarcoma who cannot be cured with radiation or surgery and who have any type of soft tissue sarcoma that would normally be treated with a cytotoxic chemotherapeutic such as doxorubicin. Olaratumab is a monoclonal antibody that targets the protein platelet-derived growth factor receptor-alpha (PDGFRA).
The molecularly targeted therapeutic niraparib (Zejula) was approved in March 2017 for use in helping to address the challenge of resistance to platinum-based cytotoxic chemotherapeutics. The agency approved niraparib for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers that are responding to platinum-based cytotoxic chemotherapeutics.
The FDA granted accelerated approval to PARP-inhibitor rucaparib (Rubraca) for treating women with advanced ovarian cancer that harbors cancer-associated BRCA1 and BRCA2 gene mutations and that has progressed despite treatment with two or more cytotoxic chemotherapy regimens.
At the same time, the FDA approved a new companion diagnostic, the FoundationFocus CDxBRCA test, to detect cancer-associated BRCA1 and BRCA2 gene mutations in ovarian cancer tissue samples and thereby identify those patients eligible for rucaparib treatment.
The molecularly targeted therapeutic ribociclib (Kisqali) for use in combination with an aromatase inhibitor for treating postmenopausal women with hormone receptor–positive, HER2–negative, advanced breast cancer was approved in March 2017. Ribociclib works by blocking the function of two specific proteins that play a role in driving cell multiplication—cyclin-dependent kinase (CDK) 4 and CDK6.
In July 2017, the FDA approved the HER2-targeted therapeutic neratinib (Nerlynx) for use as an extended adjuvant treatment for patients with early-stage HER2-positive breast cancer who have completed one year of adjuvant treatment with trastuzumab. The approval was based on results from a phase III clinical trial that showed after two years of follow-up, women with early-stage HER2-positive breast cancer who received 12 months of neratinib after one year of trastuzumab were significantly less likely to have invasive disease recurrence compared with those who received placebo.
Finally, the agency granted accelerated approval to the molecularly targeted therapeutic labeled brigatinib (Alunbrig) in April 2017, providing a new option to help patients with NSCLC harboring mutations in the ALK gene address the challenge of treatment resistance.
Brigatinib is the fourth ALK-targeted therapeutic to be approved for treating patients with metastatic NSCLC fueled by ALK mutations. Two, crizotinib and ceritinib, are approved for use as the initial treatment for patients newly diagnosed with this disease. The other two, brigatinib and alectinib, are approved only for treating patients whose cancer has either progressed after treatment with crizotinib or has failed to respond to crizotinib in the first place. Identifying the order in which the four FDA-approved ALK-targeted therapeutics should be used to provide the maximum benefit for patients is an area of intensive research investigation.
Filed Under: Drug Discovery, Oncology