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Antitumor virus shows promise against aggressive breast cancer

  • Although triple-negative breast cancer is challenging to treat, some hope may be on the horizon thanks to a cancer-killing virus called TVEC (talimogene laherparepvec).
  • In a phase 2 clinical trial, 45.9% of patients who received TVEC injections directly to the tumor during chemotherapy had no signs of cancer after surgery.
  • The next step is to conduct a phase 3 clinical trial to confirm the efficacy of TVEC for triple-negative breast cancer in a larger study population.

Triple-negative breast cancer, which accounts for 15% of newly diagnosed breast cancer cases, is characterized by tumors that lack estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) receptors.

This means that the tumor cells do not respond to hormone therapy or drugs that target HER2.

Currently, the preferred treatment approach for triple-negative breast cancer is neoadjuvant chemotherapy, a type of chemotherapy administered before the main treatment for cancer, such as surgery or radiation therapy.

Doctors administer it to shrink the size of a tumor, making it easier to remove that tumor with surgery, or to make radiation therapy more effective.

Researchers at the Moffitt Cancer Center in Florida are seeking to improve the treatment of triple-negative breast cancer by combining neoadjuvant chemotherapy with the use of a cancer-killing virus — termed an “oncolytic virus” — called TVEC (talimogene laherparepvec).

In 2021, Dr. Hatem Soliman, a medical oncologist specializing in breast cancer, and his coworkers at Moffitt Cancer Center published the findings of a phase 1 study of TVEC combined with neoadjuvant chemotherapy in patients with triple-negative breast cancer. The results demonstrated the safety and feasibility of this approach.

Now, Dr. Soliman and his team have conducted a phase 2 clinical trial to further investigate this treatment. The results of the phase 2 trial have been published in Nature Medicine.

TVEC cooperates with chemotherapy

Some patients with triple-negative breast cancer respond well to chemotherapy and have no signs of cancer in their tissues after treatment. This is known as a “complete pathological response.”

These patients are unlikely to develop cancer again in the next 5 years. Other patients do not achieve a complete response with chemotherapy and are far more likely to develop cancer in the next 2–3 years.

Researchers at Moffitt hoped to find a way to achieve a pathological complete response in patients who may otherwise respond poorly to chemotherapy.

TVEC is already approved for the treatment of advanced melanoma thanks to its ability to kill cancer cells and activate the immune system.

Dr. Soliman and his team predicted that TVEC injections into triple-negative breast cancer tumors during neoadjuvant chemotherapy would result in a higher response rate to chemotherapy, as seen in melanoma.

When asked to explain what TVEC does to the body in patients with triple-negative breast cancer, Dr. Soliman told Medical News Today:

“Talimogene laherparepvec (TVEC) is an oncolytic [cancer-killing] virus that can preferentially infect cancer cells when injected into a tumor. The virus will cause tumor cells to burst open while activating the immune system to attack surrounding cancer cells. Using TVEC in triple-negative breast cancer tumors is a way to wake up the immune system against the tumor while cooperating with chemotherapy to better eradicate the tumors.”

The phase 2 trial

In the trial, 37 patients with stage 2 or 3 triple-negative breast cancer, aged between 27 and 66 years, received five intratumoral TVEC injections with neoadjuvant chemotherapy followed by surgery.

Out of 37 patients, 16 (45.9%) achieved a complete response, that is, they had no signs of cancer after surgery. Another eight patients had a small number of cancer cells left after treatment — known as a “near-complete response.”

Out of 37 patients, 33 (89%) remained cancer-free in the 2 years after treatment, and no recurrences occurred in the patients with a complete or near-complete response.

The side effects of treatment with TVEC and chemotherapy did not differ significantly from those expected of standard chemotherapy, except for higher levels of low-grade fevers, chills, headaches, and injection site pain.

How does it compare to other treatments?

In a recent clinical trial, researchers found that patients with early-stage triple-negative breast cancer who were given a combination of pembrolizumab — a drug that helps the individual’s immune system to fight cancer by preventing the cancer cells from hiding — and neoadjuvant chemotherapy had a higher rate of full recovery compared to those who received a placebo and neoadjuvant chemotherapy.

The results of this trial led to the Food and Drug Administration’s (FDA) approval of pembrolizumab for high-risk early-stage triple-negative breast cancer.

Although this is a noteworthy development, immunotherapy with pembrolizumab or similar drugs may cause the immune system to attack healthy cells, resulting in several side effects.

Moffitt’s researchers hope that oncolytic viruses could improve the immune response against tumors without causing as many side effects as immunotherapy drugs.

Dr. Howard L. Kaufman, a surgical oncologist at Massachusetts General Hospital and lecturer at Harvard Medical School, told MNT:

“The pembrolizumab/ chemotherapy combination does have significant toxicity and the overall favorable safety profile of TVEC makes it a good agent for combination studies. The findings in the current study may also open the door for other locally delivered immunotherapy approaches as an important new area for clinical investigation into better treatments for patients with high-risk triple-negative breast cancer.”

At the moment, several oncolytic viruses are being studied as a potential treatment for cancer in clinical trials. A phase 1 trial is evaluating the use of a genetically modified smallpox virus, CF33-hNIS or VAXINIA, as a monotherapy or in combination with pembrolizumab to treat metastatic or advanced solid tumors.

Next steps

So far, phase 1 and phase 2 trials with TVEC have shown promising results. The next step is to conduct a phase 3 clinical trial to confirm the efficacy of TVEC for triple-negative breast cancer among hundreds of people.

“While the results of this study are very important for establishing a possible role for TVEC in combination with chemotherapy for neoadjuvant treatment of high-risk triple-negative breast cancer, a larger study is needed with longer follow-up to see the full impact of the therapeutic intervention on survival endpoints,” said Dr. Kaufman.

“Such studies are expensive to perform in terms of both time and money, but the current study provides a strong rationale for supporting such a future clinical trial,” he noted.

Dr. Soliman told MNT it would take 2–3 years for the phase 3 trial to be done and TVEC to become available to patients with triple-negative breast cancer.

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