Merck this morning announced that a combination of its drug pembrolizumab (Keytruda) and chemotherapy succeeded in a Phase 3 study in breast cancer, a potentially notable advance for immunotherapy in treating the disease.
Merck (NYSE: MRK) said that Keytruda and chemotherapy beat chemo alone when given to patients with triple-negative breast cancer in a study called Keynote-522. The regimen was administered during what’s known as the neoadjuvant setting, before patients have surgery to remove a tumor.
Without providing details, Merck said that Keytruda-chemo led to a statistically significant improvement in pathological complete responses for these patients—that is, there was no trace of cancer on tissue samples taken after therapy and surgery. The 1,174-patient study will now continue to see if the regimen hits its other main goal, event-free survival—whether the combination delays disease progression or death. Patients in the trial are getting a combo of either Keytruda and chemo or just chemo before surgery, and then either Keytruda or placebo following the surgery.
Merck added that the results were seen regardless of how much of the protein PD-L1 was expressed on patients’ tumors, a marker for response to immunotherapies like Keytruda. The company didn’t see any surprising safety signals. Merck will “discuss the data with health authorities” and share the details at a future medical meeting, said Merck executive vice president Roger Perlmutter, in a statement.
The news is noteworthy because it marks the first time that an immunotherapy known as a checkpoint inhibitor has succeeded as a neoadjuvant treatment in breast cancer. Though checkpoint inhibitors have helped change the way a number of cancers are treated, they have had a tougher time making a similar type of impact in breast cancer. As Xconomy explained in May, breast cancer’s biological complexity and the availability of other treatments have presented a challenge for checkpoint inhibitors, which work by shutting down a mechanism that tumors use to hide from the immune system.
There are four main subtypes associated with certain proteins or hormones: Triple-negative breast cancer (TNBC), HER2-positive, and two forms of estrogen-receptor (ER)-positive disease. The one area thus far where immunotherapy has broken through is TNBC, an aggressive form of the disease which primarily afflicts younger women and accounts for 15 to 20 percent of cases.
TNBC tumors are thought to be more immunologically “hot,” or recognizable to the immune system, and thus the easiest breast cancer targets for immunotherapy. Earlier this year, the FDA approved the Roche drug atezolizumab (Tecentriq) and chemotherapy for a subset of TNBC patients, the first approval for immunotherapy in breast cancer.
Merck’s Keynote-522 represents the latest advance. It is one of several additional immunotherapy studies underway in neoadjuvant TNBC. Companies are also assessing a variety of regimens testing checkpoint inhibitors with other cancer drugs, like PARP inhibitor and CDK4/6 inhibitors, which may make tumors more susceptible to immunotherapy.