A pair of clinical trials show that two "smart bomb" drugs present new hope to women with aggressive breast cancers. Both medications are antibody-drug conjugates, consisting of a chemo drug that's been wedded to an antibody that bears the chemotherapy straight to cancer cells. "That's a way to take the chemo right to the cancer cells and spare the rest of the body a lot of toxicity," stated Dr. Shanu Modi, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City. "The antibody takes the chemo right to the cancer cells. When the antibody finds its target, the whole complex gets internalized into the cell, and then the chemo gets released inside the cancer cell." [tweet_embed] June 8, 2022[/tweet_embed] Modi worked as lead researcher for the first drug, Enhertu (trastuzumab deruxtecan), which delayed cancer progression for almost double the time of standard chemotherapy – 10.1 versus 5.4 months – in a select group of patients with developed breast cancer. The other drug, Trodelvy (sacituzumab govitecan), further resulted in longer progression-free survival compared to standard chemotherapy in certain cancer patients, according to results shown Saturday at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago. Such research is deemed preliminary until published in a peer-reviewed journal. Both antibody-drug conjugates are already U.S. Food and Drug Administration-approved for use in treating particular types of breast cancer. These new clinical trials reveal that they could be useful for even more patients, announced ASCO Chief Medical Officer Dr. Julie Gralow. Enhertu is already approved in over 40 nations for the treatment of adult patients with HER2-positive breast cancer, the researchers announced in background notes. Human epidermal growth factor receptor 2 (HER2) is a protein that stimulates the development of cancer cells. Roughly one in five breast cancers have extra copies of the gene that makes the HER2 protein; those cancers tend to be more aggressive. [tweet_embed] June 8, 2022[/tweet_embed] The tastuzumab part of Enhertu is an antibody that steers the drug to HER2 receptors, Modi presented, making it very useful in breast cancers that are driven by HER2. Though researchers had reason to believe the drug might further be effective in treating patients whose breast cancer expresses little HER2. "Once it's released inside the target cancer cell, the drug can now pass through the membrane of the cells and it can enter neighboring cells which may not have that target protein," Modi stated. Thus, even low levels of HER2 can still help direct the chemo to where it's needed most. For this clinical trial, researchers recruited 557 patients in Asia, Europe and North America whose breast cancers were HER2-low and either inoperable or had spread to other organs. All had already undergone chemotherapy once or twice. Patients were randomly assigned on a two-to-one basis to receive either Enhertu or a doctor-chosen chemo drug. Results revealed that progression-free survival almost doubled in Enhertu patients versus those who got standard chemo. They further had a higher overall survival rate of roughly 24 months compared to 17 months. "This is important because this is a very common kind of breast cancer, probably three times as common as the group that we were already using this drug for," said co-researcher Dr. Hal Burstein, a medical oncologist with Dana-Farber Cancer Center, in Boston. [tweet_embed] June 8, 2022[/tweet_embed] Enhertu was further less toxic than chemo, with roughly 53% of patients suffering adverse events versus 67% of those treated with chemotherapy alone. "Importantly, this antibody drug conjugate compared to standard chemo is actually less toxic," Gralow stated of Enhertu. "So it's a clear winner both in terms of efficacy as well as toxicity. This absolutely will change the standard of care." Based on these results, the FDA in April granted "breakthrough therapy designation" for Enhertu for use against HER2-low breast cancers.