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Combination Care for Cancer

Medically Reviewed by Michael W. Smith, MD on January 11, 2021

Immunotherapy helps your immune system fight cancer. It’s a newer form of cancer treatment than chemotherapy, which uses drugs that directly attack cancerous cells.

The FDA has approved immunotherapy for more than two dozen types of cancers. But many people don’t respond to immunotherapy or don’t do well on it alone.

Researchers are testing ways to combine immunotherapies. For example, they may mix two drugs, try one after the other, or add immunotherapy to traditional cancer treatments. The goal is to find the combination care that has the best chance of treating your cancer.

How Immunotherapy Pairings Work

Tackling cancer with more than one type of treatment may work better than one alone. That may give you a better shot at staying cancer-free or living longer. Combination care may be especially helpful with cancers that are advanced or harder to treat, such as lung cancer or melanoma.

Combinations may help to:

  • Rev up your immune response to the cancer
  • Prevent cancer cells from “hiding” from your immune system
  • Cut down the number of cancer cells or the size of the tumors

Different combinations of immunotherapies may interact to fight back against cancer in new or more powerful ways. Doctors also pair immunotherapies with traditional cancer treatments such as chemotherapy or radiation.

Checkpoint Inhibitors

Since 2006, researchers have launched more than 3,300 trials to test just one type of immunotherapy called checkpoint inhibitors. These are drugs that open “checkpoints” that cancer cells hide behind to evade attacks from your immune system.

More than three out of four immunotherapy trials today are testing checkpoint inhibitors with other types of treatment. This approach may help shrink many types of cancer. The treatment may work longer and with fewer side effects than some other types of cancer treatment.

The FDA has approved more than a dozen combinations of checkpoint inhibitors for different types of cancers. The first FDA-approved pairing of two immunotherapies was 2 checkpoint inhibitors (ipilimumab plus nivolumab).

Doctors have used this combo for melanoma for many years. It has helped even in cases where the cancer has spread to the brain.

The FDA also approved ipilimumab and nivolumab:

  • As a first treatment for advanced kidney cancer
  • For certain cases of advanced colorectal cancer
  • For the most common type of liver cancer
  • For advanced non-small-cell lung cancer

More approvals of this combo are likely on the way for other types of cancer. This includes ovarian cancer and mesothelioma. Researchers will be watchful. That’s because ipilimumab can lead to severe side effects.

Immunotherapy Plus Chemotherapy

Another approach to combination care is to add immunotherapy to another type of cancer treatment. One example is to treat breast or pancreatic cancer with a mix of immunotherapy and chemotherapy drugs such as cisplatin and Taxol.

Breast cancer. It doesn’t trigger a strong immune response. That made breast cancer a poorer choice for immunotherapy alone. But pairing it with chemo may improve those odds. Based on good trial results, the FDA approved the first immunotherapy combination for one type of breast cancer. This was a combo of a checkpoint inhibitor plus Taxol.

Pancreatic cancer. Early results from a trial called PRINCE have been promising. It looked at how combining chemotherapy with two types of immunotherapy helped people whose pancreatic cancer had spread.

Lung cancer. Pairing immune-boosting drugs with chemotherapy drugs has helped some people whose lung cancer has spread. The FDA has approved more than one combination care for this cancer.

Blood cancers. T cells help your immune system fight disease. CAR T-cell therapy changes T cells so they can spot and fight cancer cells better. This type of treatment has worked really well for many people with blood cancers such as leukemia. Another recent trial tried a chemotherapy drug and a checkpoint inhibitor on people whose leukemia had come back or stopped responding to treatment. People did twice as well on combination therapy than on chemotherapy by itself.

Cervical cancer. Cancer can spread to lymph nodes in women with cervical cancer. The tumors often return even after both chemotherapy and radiation. Researchers recently tested following chemoradiotherapy with ipilimumab and found that it seemed to help and is safe. Nearly twice as many women were alive after 1 year under the combination therapy than with chemoradiotherapy alone.

Immunotherapy Plus Targeted Therapy

Chemotherapy drugs don’t distinguish between cancerous and healthy cells. Targeted therapy uses medications that target the faulty parts inside the cancer cells to stop or slow their growth. Kidney cancer treatment is one area where a targeted therapy called a VEGF inhibitor is being combined with immunotherapy.

In recent years, the FDA has approved:

  • A checkpoint inhibitor and targeted therapy for endometrial cancer.
  • A checkpoint inhibitor, targeted therapy, and chemotherapy for lung cancer.

 

Immunotherapy With Surgery

The combined strategy of immunotherapy and surgery may help shrink tumors as well as prompt your body to release “attacker” cells to reach smaller tumors.

In one recent study, people who  had recurrent brain cancer lived almost twice as long if they received immunotherapy before and after their surgery, compared to those who had immunotherapy once, before their operation.

Recent research has also shown that immunotherapy before surgery may greatly shrink colon tumors and oral cancer. A large number of trials continue.

Immunotherapy and Radiation Therapy

Radiation shrinks cancers. It can also change your body’s immune response. This has encouraged researchers to pair it with immunotherapy to make cancer treatments more potent. But more research is needed to know if and how much it might help.

WebMD Medical Reference

Sources

SOURCES:

National Cancer Institute: “Immunotherapy to Treat Cancer,” “Targeted Therapy-Immunotherapy Combinations Effective for Advanced Kidney Cancer,” “FDA Approves Nivolumab and Ipilimumab Combination for Advanced Kidney Cancer,” “Combination of Immunotherapy Drugs Approved for Metastatic Colorectal Cancer.”

Gordon J. Freeman, PhD, professor of medicine, medical oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston.

Journal of Oncology: Combinatorial Approach to Improve Cancer Immunotherapy: Rational Drug Design Strategy to Simultaneously Hit Multiple Targets to Kill Tumor Cells and to Activate the Immune System.”

Cancer Research Institute: “What Is Immunotherapy?” “PD-1/PD-L1 Landscape,”

Cancer Immunotherapy in 2020 and Beyond,” “Timeline of Progress.”

The BMJ: “Combination immunotherapy: the emerging treatment that removes cancer’s ‘cloak of invisibility.’”

MD Anderson: “Immunotherapy combination is greater than the sum of its parts” “What is CAR-T cell therapy?”

Nature Reviews Drug Discovery: “Trends in clinical development for PD-1/PD-L1 inhibitors.”

Nature Medicine: Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers.

FDA: “FDA grants accelerated approval to nivolumab and ipilimumab combination for hepatocellular carcinoma,” “FDA grants nivolumab accelerated approval for third-line treatment of metastatic small cell lung cancer.”

Discoveries: “Immunotherapy for Breast Cancer: First FDA Approved Regimen.”

Cancer Discovery: “Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/Refractory Acute Myeloid Leukemia: A Non-randomized, Open-label, Phase 2 Study.”

JAMA Oncology: Sequential Ipilimumab After Chemoradiotherapy in Curative-Intent Treatment of Patients With Node-Positive Cervical Cancer.

Dana-Farber Cancer Institute: “Timing of immunotherapy nearly doubles survival rate in brain cancer patients,” “Pre-operative immunotherapy shows promise in oral cancers.”

Journal of Experimental and Clinical Cancer Research: “Advances in cancer immunotherapy 2019 -- latest trends.”

Molecular Oncology: “Radiotherapy-immunotherapy combinations -- perspectives and challenges.”

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