Opdivo (Nivolumab)

What Is Opdivo?

Opdivo is an immunotherapy drug used to treat a variety of cancers. Its generic name is nivolumab.

In October 2020, the U.S. Food and Drug Administration approved Opdivo and Yervoy (ipilimumab) for mesothelioma. It is intended for the first-line treatment of inoperable malignant pleural mesothelioma in adults.

The FDA had previously approved nivolumab in 2015 as a second-line treatment – and the first immunotherapy drug – for advanced non-small cell lung cancer. Opdivo demonstrated survival benefits over three years during the CheckMate 743 clinical trial. Among mesothelioma patients in the trial who received nivolumab with ipilimumab, 23% were alive at three years compared to 15% treated with chemotherapy.

This combination [Opdivo and Yervoy] is a game-changer, showing unquestionable survival benefits for mesothelioma. It confirms that the disease is subject to the harnessing of the immune system. This will open many doors.

Dr. Bernardo Goulart

Medical Oncologist at Seattle Cancer Care Alliance

At the three-year follow-up of CheckMate 743 and approximately one year off mesothelioma treatment, more patients who responded to Opdivo plus Yervoy remained in response than those treated with chemotherapy.

The duration of response was longer with the dual immunotherapy combination regardless of mesothelioma cell type. The manufacturer, Bristol Myers Squibb, reported that patients who responded to nivolumab plus ipilimumab remained in response at three years compared to no patients in the chemotherapy arm.

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How Does Opdivo Work?

Opdivo is an immune checkpoint inhibitor that works with the T cells of your immune system to recognize and attack threats such as cancer cells.

Cancer cells can sometimes disguise themselves and hide from T cells, allowing tumors to grow faster and spread quicker, using the PD-1 pathway. Many cancer cells have high expressions of the PD-L1 protein. This protein can fool T cells into thinking the cancer cells are healthy cells, thus inhibiting the immune system response.

Nivolumab essentially blocks cancer’s ability to disguise itself. This in turn activates T cells to attack, resulting in decreased tumor growth. 

The immunotherapy drug Yervoy is an anti-CTLA-4 antibody that promotes the growth of T cells. Together with Opdivo, the medications are a potent combination that prohibit cancer cell protection and elevate T-cell activity.

Opdivo and Yervoy for Mesothelioma

The positive results of the CheckMate 743 clinical trial led to the FDA’s approval of Opdivo and Yervoy for mesothelioma. 

Each medication harnesses the patient’s immune system in a different way to target cancer cells. Opdivo blocks the signal that prevents T cells from identifying and attacking tumors. Yervoy targets the CTLA-4 protein receptor, which, together with PD-1, inhibits T cell activation. 

After nivolumab exposes cancer cells to the immune system, ipilimumab stimulates immune activity, upregulating T-cell production and effectiveness. This combined effect creates a synergistic mechanism more efficient than either drug alone.

Side Effects of Opdivo

PD-1 is a checkpoint protein found on T cells. It works as an off switch, keeping T cells from attacking other cells in the body.

Opdivo inhibits PD-1, allowing T cells to recognize and attack deceptive cancer cells. However, Opdivo can also cause T cells to attack the healthy cells of organs and tissues throughout the body, affecting how they work.

Nivolumab can cause side effects on its own or in combination with ipilimumab. Immune-mediated reactions, or disruptions to the immune system, cause the most severe side effects of nivolumab and other checkpoint inhibitors such as pembrolizumab (Keytruda).

Common Side Effects of Opdivo

In clinical trials, the most common side effects of nivolumab when used alone were fatigue, lymphocytopenia (low white blood cells), low sodium, decreased appetite and pain in the muscles, bones and joints.

Other common adverse effects such as shortness of breath and cough can mirror symptoms of lung cancer or pleural mesothelioma.

Most patients do not experience all the common side effects, and most side effects are reversible or regress after treatment is complete.

Rare Side Effects of Opdivo

Rare side effects of Opdivo occur in less than 4% of patients and can become life-threatening. These reactions happen when Opdivo causes severe inflammation in an area, which leads to scarring and tissue damage.

Opdivo is delivered via IV injection. In rare cases, this may lead to severe infusion reactions such as fever, dizziness, itching, rash and chills or shaking.

Opdivo and Yervoy Side Effects

Opdivo and Yervoy for mesothelioma can introduce new adverse reactions. Mild side effects such as hormone imbalance may be more severe with the combination. While some side effects are reversible, others could become permanent. 

Patients on nivolumab and ipilimumab may experience pneumonitis or joint inflammation that requires immunosuppression with prednisone or other steroids. However, prolonged corticosteroid use can decrease the immune response and cause vision or blood sugar changes.

Mesothelioma Clinical Trials Involving Opdivo

Researchers worldwide are studying Opdivo as a single therapy and in combination with other drugs to treat mesothelioma.

New Study Open to Peritoneal Mesothelioma Patients

Peritoneal mesothelioma patients eligible for surgery may be candidates for a new clinical trial at The University of Chicago. The study will determine the effects of treating peritoneal mesothelioma with nivolumab and ipilimumab before and after surgery. 

Researchers hope to learn whether the immunotherapy combination will decrease the number of cancer cells that linger after surgery. The treatment delays the time it takes for cancer to regrow, which may benefit patients. 

The trial is in phase II and is estimated to be complete by June 2025. Participants will receive treatment for two years and regular follow-ups for 42 months. Patients must have no history of pneumonitis, be otherwise healthy and be eligible for hyperthermic intraperitoneal chemotherapy, also known as HIPEC.

Neoadjuvant Trial Enrolling Surgical Pleural Mesothelioma Patients

In 2019, researchers at Johns Hopkins University launched a study to determine if nivolumab and ipilimumab could benefit pleural mesothelioma patients before surgical resection. 

Doctors will administer the combination immunotherapy treatment for one year following standard modalities. The study will follow patients for up to five years and determine whether the treatment is safe and effective. 

To qualify, pleural mesothelioma patients must be surgical candidates and have epithelial or biphasic histology. Participants must also have adequate organ function, no history of prior immunotherapy treatment and be otherwise healthy.

CheckMate 743 Phase III 

Bristol Myers Squibb sponsored the phase III CheckMate 743 clinical trial and began enrolling participants in 2016. It aimed to include 600 mesothelioma patients across 20 countries, making it one of the most extensive mesothelioma-specific immunotherapy clinical trials undertaken.

Prominent U.S. cancer centers with mesothelioma specialty programs, including Moffitt Cancer Center in Tampa and the Mayo Clinic in Rochester, Minnesota, are among the investigational sites currently engaged in such clinical trials.

In the randomized trial, the nivolumab and ipilimumab combination is tested against a pemetrexed and cisplatin or carboplatin chemotherapy combination — the current standard of care regimen for mesothelioma patients. 

Compared to chemotherapy, patients who received Opdivo and Yervoy during CheckMate 743 had an 8% higher three-year survival rate and a four-month longer median overall survival.

French Study Shows Promise

Perhaps the most impressive results came from the 2017 American Society of Clinical Oncology annual meeting in Chicago. A multicenter phase II trial in France included 125 patients with recurrent mesothelioma and measured the effectiveness of Opdivo with Yervoy.

Opdivo alone and in combination with Yervoy resulted in a disease control rate — the percentage of patients in which cancer either does not grow or shrinks — of 50% for those getting the drug combination and 44% for those receiving only nivolumab. Previous studies using other second-line treatments are usually under 30%.

According to study results presented at the ASCO meeting, tumors shrank in 26% of patients receiving the combination and 17% of patients receiving the single drug. The progression-free survival (until cancer worsens) was 5.6 months for Opdivo with Yervoy and four months for nivolumab alone.

“Both Opdivo alone and Opdivo plus ipilimumab reached their [primary] endpoint in second-and third-line MPM patients, increasing the 12-week DCR,” said lead researcher Dr. Arnaud Scherpereel. 

“Moreover, patients from both arms of this study seem to have prolonged median [overall survival] than all previous reports in this setting,” Scherpereel said. “Immunotherapy may provide new therapeutic options as a second- and third-line treatment for patients [with relapsing malignant pleural mesothelioma].”

Dutch Study Paved the Way

In 2015, scientists at the Netherlands Cancer Institute in Amsterdam began the first mesothelioma clinical trial for Opdivo, finding promising results. The study included 38 patients with recurrent pleural mesothelioma and met the primary goal of improving the three-month disease control rate between 20% to 40%.

“The toxicity was mild, and long-lasting results were observed. A clear correlation between PD-L1 expression and response was observed,” lead researcher Josine Quispel-Janssen concluded.

In this aggressive cancer that historically has had limited treatment options, we’ve now not only seen the potential for patients to live longer with nivolumab plus ipilimumab but … these results give us further proof of the durability of the outcomes achieved with this combination.

Dr. Solange Peters

Thoracic Oncology, Lausanne University Hospital, Switzerland

Questions to Ask Your Doctor

Your health care team or pharmacist can provide you with more information about Opdivo or combination therapy with Opdivo and Yervoy for mesothelioma. Let your doctor know if you plan to become pregnant or have a history of any concerning medical issues.