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AACR Annual Meeting 2017: Expanding HER2 Therapy

Can HER2-targeted therapies be successful across multiple cancer types? It’s complicated. Kate Yandell

At one time, HER2-positive breast cancer was seen as an especially challenging disease to treat, said medical oncologist and researcher Howard Burris of the Sarah Cannon Research Institute in Nashville, Tennessee. Burris commented during a session on “Precision Medicine Clinical Trials” held at the American Association for Cancer Research (AACR) Annual Meeting 2017 on April 2.

Herceptin (trastuzumab), a targeted therapy approved by the U.S. Food and Drug Administration in 1998 to treat HER2-positive breast cancer, changed that, Burris said. Now there are several targeted therapies approved to treat HER2-positive breast cancer, and Herceptin is approved to also treat HER2-positive gastric cancer. But HER2 genes are altered in other cancer types. Two trials whose results were presented during the precision medicine session are testing HER2 therapies against more cancer types. 

The phase II SUMMIT trial tested the investigational drug neratinib in patients with a variety of cancer types. In the past, HER2-targeting drugs have been approved for patients whose tumors have too many copies of the HER2 gene. For the SUMMIT trial, the researchers sought participants whose tumors had mutations in the HER2 gene. (The trial also included patients with mutations in the HER3 gene, but these patients’ cancers did not respond to the treatment.)

As part of the trial, 124 patients with HER2-mutated cancer were given neratinib. Patients with breast cancer were most likely to respond to the drug, and preliminary results in cervical and biliary cancers were encouraging, said David Hyman, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City who led the trial. But patients with bladder and colorectal cancers showed little response. Most patients with non–small cell lung cancer also didn’t see their tumors shrink on the therapy, but in some, the tumors did remain stable on the drug.

Patients in the trial had 35 different mutations to the HER2 gene. Some mutations were associated with a better response to the drug than others. “These data show that you can’t treat all HER2 mutations the same,” said Hyman. But having a certain mutation did not mean that a patient would respond regardless of cancer type. “I don’t think that we are ready to reorganize the taxonomy of cancer by mutation alone,” said Hyman, who spoke at a press conference held at the Annual Meeting April 2.

Hyman also pointed out that one breast cancer patient whose tumor responded to neratinib had a mutation that has never been observed in anyone else, to his knowledge. “I think this raises the possibility that there are certain patients who will have truly private genetic alterations that may be true one-off events, and yet that can be the driver of their cancer,” Hyman said.

Hyman said that HER2 could be targeted more effectively in more situations by testing the right combinations of drugs.

A combination of HER2-targeted drugs did have some success in another trial presented in the same precision medicine session and at the same press conference. The HERACLES trial combined Tykerb (lapatinib), approved for HER2-positive breast cancer, with Herceptin, testing the combination in a small subset of metastatic HER2-positive cancer whose tumors had a specific genetic profile and who were not responding to standard care. Of 33 patients who received the combination HER2 therapy, 10 responded, experiencing significant tumor shrinkage, and 13 had stable disease, said Silvia Marsoni of the Candiolo Cancer Institute in Italy, who presented the trial results. One patient has no evidence of disease after three years on the combination. 


Kate Yandell is the associate editor of Cancer Today.

04/03/2017
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