New Cancer 'Missile' Drugs May Be More Effective Than Traditional Chemotherapy

The Food and Drug Administration (FDA) recently approved a “guided missile” drug to target a type of ovarian cancer. This new drug, which belongs to a class of medicines called antibody-drug conjugates, delivers chemotherapy directly to cancerous cells while avoiding healthy cells in the body.

The treatment, Elahere (mirvetuximab soravtansine), is for patients with late-stage disease who have tried up to three previous cancer therapies. Drugmaker AbbVie says these patients often undergo surgery and then are treated with chemotherapy. But they can become resistant to that chemotherapy and require another treatment option.

“These patients previously had very limited options and Elahere changes that,” Kathleen Moore, MD, a gynecologic oncologist and associate director of clinical research at the Stephenson Cancer Center of the University of Oklahoma, said in a press release.

In clinical trials, patients who received the antibody-drug conjugate had increased overall survival rates. Elahere reduced the risk of cancer progression by 35% compared to conventional chemotherapy.

Data from the Phase 3 trial found that patients receiving Elahere had fewer severe side effects and a lower rate of stopping the treatment due to adverse events compared to participants undergoing chemotherapy.

The new ovarian cancer treatment is just one in a line of antibody-drug conjugates for cancer treatment, which experts say is a promising new area of targeted cancer therapy. 

What Are Antibody-Drug Conjugates?

Most chemotherapy treatments are given systemically, meaning they impact the entire body. 

Antibody-drug conjugates deliver high doses of medicine directly to cancerous cells, which can help protect other cells in the body from the effects of chemotherapy. This, in turn, can reduce drug side effects and result in potentially more effective treatment. 

Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the MD Anderson Cancer Center at the University of Texas, told Verywell that antibody-drug conjugates essentially work like this: An antibody that targets cancer cells is connected via a “linker” protein to a cancer-killing drug such as chemotherapy. When the medication is administered to a patient intravenously, it goes to the targeted cancer site, killing the cancerous cells without harming the non-cancerous ones. 

“Because this is more targeted therapy, we can give higher amounts of chemotherapy to the cancer cells,” Meric-Bernstam said. “And, what’s really exciting is that the new chemotherapy classes that are being developed are a lot more potent. So with antibody-drug conjugates, we can give a lot higher concentrations of chemotherapy to the cancer cells than we would be able to if we delivered it through [conventional chemotherapy] IV, where all cells would see the same amount of the toxic agent.”

What’s more, Meric-Bernstam said that newer generations of antibody-drug conjugates are also able to affect the neighboring cancer cells around a targeted tumor. This creates a “bystander effect” that can make the drugs more impactful.

Who Are Antibody-Drug Conjugates For?

So far, clinical trials of antibody-drug conjugates have been focused on advanced-stage disease, Meric-Bernstam said. This means they’re for patients who have metastatic cancer, or cancer that cannot be removed with surgery. 

But as more research is conducted, antibody-drug conjugates might be useful for earlier stages of cancer, too.

“As we show efficacy of a drug in an advanced setting, then we start looking at earlier lines of metastatic settings. Then, ultimately, we start looking at the efficacy in patients who have operable or potentially curable disease to try to see if we can be even more effective than standard therapy,” Meric-Bernstam said. “That’s sort of the evolution for each antibody-drug conjugate that comes into development.”

Brad McGregor, MD, director of clinical research at the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, told Verywell he is researching how using two antibody-drug conjugates together might be more effective in treating bladder cancer. His recent Phase 1 trial showed the combination of two drugs showed high efficacy and was reasonably well tolerated in patients.

“Now the thought is, maybe we can be doing that with other cancers, too,” he said.

What Are the Side Effects and Risks of Antibody-Drug Conjugates?

Like with conventional chemotherapy treatment, antibody-drug conjugates have side effects. But, unlike many cancer therapies that affect all cells, including healthy ones, antibody-drug conjugates aim to limit the toxic effects of chemotherapy in the body by focusing specifically on cancer cells. 

Side effects of antibody-drug conjugates vary depending on the antibody and potency of chemotherapy used but can include a drop in white blood cell count, blurred vision, peripheral neuropathy, and low platelet count.

Research has found that side effects of antibody-drug conjugates for breast cancer include nausea and vomiting, hair loss, diarrhea, left ventricular dysfunction (weak heart pump), and pneumonitis (inflammation of the lung tissue).

“It’s really important that the treating physicians are aware of the side effects and patients learn what they need to be watching out for so they can communicate with their doctors to make sure we’re delivering these drugs safely,” Meric-Bernstam said.

And even though antibody-drug conjugates intend to limit the harm to healthy cells, they are not perfect.

“Some [antibody-drug conjugates] linkers are really stable, and the chemotherapy only gets released at the site,” McGregor said. “Other linkers are slightly more unstable… and some of the chemotherapy may get released from the antibody early before actually hitting those cancer cells. That is where that linker—how those antibodies are attached to the chemotherapy—is really, really critical.”

What Antibody-Drug Conjugates Are Already In Use?

There are currently more than a dozen FDA approvals for antibody-drug conjugates, including ones to treat lymphoma, breast cancer, bladder cancer, lung cancer, and ovarian cancer, McGregor said.

Research from various drugmakers has shown that some patients might live longer or have better outcomes if their cancer is treated with an antibody-drug conjugate compared to conventional (systemic) chemotherapy. 

Studies of Padcev (enfortumab vedotin), an antibody-drug conjugate for advanced bladder cancer, found that patients receiving the medication plus pembrolizumab (a type of immunotherapy) might live twice as long as patients who were given chemotherapy.

Polivy (polatuzumab vedotin), an antibody-drug conjugate for lymphoma, was shown to reduce the risk of cancer worsening or returning by 27% when paired with R-CHP (a combination of medicines) compared with traditional chemoimmunotherapy.

According to a 2023 review on antibody-drug conjugates, this area of cancer treatment is very promising due to its ability to deliver very potent and targeted chemotherapy.

“Antibody-drug conjugates allow us to really optimize the delivery of chemotherapy to where we want it to be,” McGregor said.

This does not mean that a patient isn’t getting the best treatment if they are receiving systemic chemotherapy or another medicine, McGregor said. Cancers vary, as do patients’ needs, and it’s important to remember that these new drugs are not a silver bullet.

“We are still trying to figure out how best to incorporate these [antibody-drug conjugates] into therapy,” McGregor said. “In some cancers, they’re ready and they’re the new standard of care before chemotherapy. But in some situations, systemic chemotherapy is still the standard. Antibody-drug conjugates are a novel way to improve chemotherapy delivery, but their role is still evolving.”