Attacking cancer with a range of drugs and treatments

Cancer cells survive largely because of their ability to adapt to their environment, and this includes fending off an attack from some cancer treatments. One drug can target a genetic mutation in a cancer cell, but another mutation can control tumor growth and cause it to grow. Another drug could shut down the signaling pathway that allows cancer cells to grow, but a tumor could find a new way to communicate and survive. As the cancer adapts to treatments, drug resistance and/or relapse can occur.

One way clinicians and researchers try to prevent such relapses and resistance before they occur is by using combination drug therapies designed to attack cancer cells at multiple levels. For example, the US Food and Drug Administration (FDA) approved the use of two targeted therapies in July: the drugs neratinib (Nerlynx® ^{) and} trastuzumab (Herceptin® ), which together can reduce the risk of relapse in women with HER2-positive breast cancer. In this case, neratinab is an adjuvant therapy, given after the initial treatment to reduce the risk of the cancer coming back. Scientists in the UK and Ireland who conducted research into the drug pairing say that “the results showed that the combination of trastuzumab and neratinib was significantly more potent” than trastuzumab alone in certain cases of HER2-positive breast cancer.

Looking for new groups

The discovery of precise cancer treatments, such as targeted therapy and immunotherapy drugs, provides dozens of new formulations to explore. “Immunotherapy drugs called checkpoint inhibitors are generally used on their own,” says Ankur Parikh, MD, medical director of the Center for Advanced Individual Medicine and a hematologist, oncologist, and medical oncologist at our Hospital in Philadelphia. “But now, with these promising data, combination therapy is being explored. Data using radiation combined with anti-PD-1 therapy in patients with brain metastases associated with melanoma has been published. Checkpoint inhibitors in combination with radiotherapy in lung cancers are also being explored. “. In fact, the US Food and Drug Administration has approved the checkpoint inhibitor pembrolizumab (Keytruda® .) ^.) in combination with the chemotherapy drugs pemetrexed and carboplatin as first-line treatment for patients with a certain type of metastatic non-small cell lung cancer.

Doctors have been using a combination of drugs and treatments that include targeted therapy and immunotherapy drugs for several years. For example, in 2009, the U.S. Food and Drug Administration approved the targeted therapy drug bevacizumab (Avastin® ⁾ in combination with interferon-alpha, an immunotherapy known as a cytokine, to treat kidney cancer. In 2015, the FDA approved the checkpoint inhibitor combination nivolumab (Opdivo® ⁾ and ipilimumab (Yervoy® ⁾ to treat some patients with metastatic melanoma.

In theory, these groups attack different receptors, enzymes, or pathways, blocking the cancer cells’ ability to escape the immune system or resist treatment. For example, checkpoint inhibitors are immunotherapy drugs designed to block the receptors that are used to send signals that allow cancer cells to hide from the immune system. Immune cells check other cells at certain checkpoints to determine if they are good, healthy cells or if they pose a threat, such as an infection. If not for these checkpoints, the immune system could attack healthy cells. Nivolumab targets a checkpoint receptor called PD-1; ipilimumab targets the CTLA-4 receptor. The two drugs worked for some patients when used alone, but some melanoma patients did better when the drugs were combined to target both receptors. Combining checkpoint inhibitors with other medications can also improve their ability to attack and kill cancer.

Treatments and times

The challenge for researchers is to find the right combinations of drugs, treatments, and times. What medications or treatments will work well together? Should they be given together or separately? What medication or treatment should be given first and for how long? The answers can be discovered in dozens of clinical trials exploring combinations of cancer drugs and treatments. Another challenge, Dr. Barrick says, is how medications affect a patient’s overall health and quality of life. “When the treatments are combined, the side effects are often combined. We also don’t know the effect of immunotherapy on the side effects of other treatments.” In some patients, immunotherapy drugs can cause the immune system to attack healthy cells, causing serious side effects such as autoimmune disease, flu-like symptoms, and even death.

In fact, in July, the Food and Drug Administration suspended two trials that combined pembrolizumab with other drugs to treat multiple myeloma after several patients died. However, studies of the drugs and treatment combinations are very promising, and researchers continue to explore new drug combinations in search of better outcomes for cancer patients. An article in the journal Clinical and Translational Science captured the mood of many researchers when it suggested that “combined therapies can significantly improve outcomes for cancer patients, and such treatments are certainly expected to eventually become the standard of care for cancer treatment.”

Find out how the development of cancer treatments can provide more accurate solutions.