FDA Approvals Provide Advances for a Range of Cancer Types
During late spring and early summer, the U.S. Food and Drug Administration (FDA) approved four new molecularly targeted therapeutics—alpelisib (Piqray), polatuzumab vedotin-piiq (Polivy), selinexor (Xpovio), and darolutamide (Nubeqa)—for treating certain patients with a wide array of cancer types. Molecularly targeted therapeutics are the cornerstone of precision oncology. So, this flurry of approvals highlights that progress in this important area of cancer care is continuing unabated.
A new molecularly targeted therapeutic for treating breast cancer
Alpelisib targets phosphatidylinositol 3-kinase (PI3K) alpha, which has an important role in driving cell multiplication and survival. Research has shown that mutations in the PIK3CA gene, which encodes PI3K-alpha protein, promote the multiplication and survival of about 40 percent of hormone receptor–positive, HER2-negative breast cancers.
On May 14, alpelisib became the first approved PI3K-alpha–targeted therapeutic for use in the treatment of breast cancer. It was specifically approved for use in combination with fulvestrant for treating men and postmenopausal women who have advanced or metastatic, hormone receptor–positive, HER2-negative breast cancer that tests positive for PIK3CA mutations and has progressed during or after endocrine therapy.
Targeting blood cancers
The approvals of polatuzumab vedotin-piiq on June 10 and selinexor on July 3 have provided new molecularly targeted therapeutics for treating two of the more common types of blood cancer, diffuse large B-cell lymphoma and multiple myeloma, respectively.
Polatuzumab vedotin-piiq is an antibody-drug conjugate. It comprises the cytotoxic agent monomethyl auristatin E attached to an antibody that targets CD79b, which is a protein that is found on the surface of diffuse large B-cell lymphoma cells. Polatuzumab vedotin-piiq was specifically approved for use in combination with the cytotoxic chemotherapeutic bendamustine and the immunotherapeutic rituximab for treating adults who have large B-cell lymphoma that has not responded to or has relapsed after two other treatments.
Selinexor targets a protein called XPO1, which is found at elevated levels in multiple myeloma cells. It was approved for treating patients with multiple myeloma whose disease has relapsed subsequent to, or never responded to, treatment with at least two proteasome inhibitors, at least two immunomodulatory agents, and a CD38-targeted immunotherapeutic.
Adding a new molecularly targeted treatment option for prostate cancer patients
Darolutamide targets the androgen receptor. In doing so, it deprives prostate cancer cells of the androgens (hormones such as testosterone) that fuel their growth.
On July 30, darolutamide became the third therapeutic approved by the FDA based on its ability to increase the time before early-stage prostate cancer progresses and becomes metastatic. The other two, apalutamide (Erleada) and enzalutamide (Xtandi), were approved in 2018. These three therapeutics are specifically approved for treating nonmetastatic castration-resistant prostate cancer.
By keeping metastatic disease at bay, apalutamide, darolutamide, and enzalutamide are providing men like Ron Scolamiero, who was featured in the AACR Cancer Progress Report 2018, with new hope for living a longer life.
Expanding the uses of previously approved anticancer therapeutics
In addition to the four new molecularly targeted therapeutics discussed here, during late spring and early summer, the FDA also expanded the uses of four previously approved anticancer agents as follows:
- On May 10, the antiangiogenic ramucirumab (Cyramza) was approved for treating patients who have hepatocellular carcinoma, the most common type of liver cancer, that has progressed despite treatment with another antiangiogenic called sorafenib (Nexavar). Ramucirumab was previously approved for treating certain patients with three other types of cancer, colorectal, lung, and stomach cancers.
- On May 14, the immunotherapeutic avelumab (Bavencio) was approved for use in combination with the antiangiogenic axitinib (Inlyta) for the initial treatment of patients who have advanced renal cell carcinoma, the most common type of kidney cancer. Avelumab was previously approved for treating certain patients with two other types of cancer, bladder cancer and Merkel cell carcinoma.
- On May 28, the molecularly targeted therapeutic lenalidomide (Revlimid) was approved for use in combination with the immunotherapeutic rituximab (Rituxan) for treating patients who have follicular lymphoma or marginal zone lymphoma that has progressed despite a previous treatment. Lenalidomide was previously approved for treating certain patients with two other types of cancer, mantle cell lymphoma and multiple myeloma.
- On July 30, the immunotherapeutic pembrolizumab (Keytruda) was approved for treating patients who have recurrent, locally advanced, or metastatic squamous cell carcinoma of the esophagus that tests positive for PD-L1 protein and that has progressed despite treatment with at least one other systemic therapeutic. Pembrolizumab was previously approved for treating certain patients with 11 other types of cancer, including melanoma and lung cancer, and for treating patients with any type of solid tumor characterized by the presence of MSI-high or MMR deficiency.
There are many clinical trials underway investigating whether anticancer therapeutics already approved by the FDA and in use for treating certain types of cancer can benefit patients with other types of cancer. It is likely, therefore, that there will be more expansions in the use of anticancer therapeutics in the future, and we look forward to keeping you up to date with these developments on Cancer Research Catalyst.