yourcar-logo
Search
LifestyleCarsTechnologyHealthcareHivEDMesotheliomaSclerosisDietGYMApparel

A New Hope for Patients with Relapsed Mesothelioma: How an Immunotherapy Drug Can Improve Survival and Quality of Life

A New Hope for Patients with Relapsed Mesothelioma: How an Immunotherapy Drug Can Improve Survival and Quality of Life

Malignant pleural mesothelioma (MPM) is a rare and aggressive type of cancer that affects the lining of the lungs and chest cavity. MPM is mainly caused by exposure to asbestos, a mineral fiber that was widely used in construction and industry until its ban in many countries. MPM has a poor prognosis, with a median survival of less than one year after diagnosis.

MPM is difficult to treat, as it has no specific symptoms and is resistant to most conventional therapies, such as surgery, chemotherapy and radiation. Therefore, there is an urgent need for new and effective treatments that can improve the survival and quality of life of patients with MPM.

This article is a summary of a new hope for patients with relapsed MPM that uses an immunotherapy drug called nivolumab to improve survival and quality of life1. The hope is based on a multicentre, double-blind, randomised, phase 3 trial that compared nivolumab versus placebo in patients with relapsed MPM. The trial also assessed the safety and tolerability of nivolumab in this setting.

The article was published in the journal The Lancet Oncology in 2021 by a team of researchers from the UK and Australia.

What is immunotherapy?

Immunotherapy is a treatment that uses substances that stimulate or enhance the immune system to fight cancer. Immunotherapy can be given as vaccines (that introduce antigens or substances that trigger an immune response), antibodies (that bind to specific targets on cancer cells or immune cells), cytokines (that modulate the activity of immune cells) or checkpoint inhibitors (that block signals that prevent the immune system from attacking cancer cells).

Immunotherapy can have different effects on different people, depending on their genetic makeup and tumor characteristics. Immunotherapy can also cause side effects, such as rash, fever, fatigue or inflammation.

What is nivolumab?

Nivolumab is an immunotherapy drug that belongs to the class of checkpoint inhibitors, which are antibodies that block signals that prevent the immune system from attacking cancer cells. Nivolumab works by binding to and blocking PD-1 (a receptor on immune cells) or PD-L1 (a ligand on cancer cells or immune cells). PD-1 and PD-L1 interaction inhibits the immune system from recognizing and killing cancer cells. Nivolumab releases the brake on the immune system and allows it to attack cancer cells.

Nivolumab can be given intravenously (by injection into a vein) every two or four weeks. Nivolumab can cause side effects, such as rash, diarrhea, fatigue, infection or low blood cell counts.

What was the trial design?

The trial was a multicentre, double-blind, randomised, phase 3 trial that compared nivolumab versus placebo in patients with relapsed MPM. The trial enrolled 332 patients who had previously received one or two lines of chemotherapy for MPM and had disease progression or recurrence. The trial randomly assigned 221 patients to receive nivolumab (240 mg every two weeks) and 111 patients to receive placebo (saline solution every two weeks).

The trial followed the patients for up to 24 months or until death. The trial measured various outcomes, such as:

  • Primary outcome: The primary outcome was overall survival (OS), which is the time from randomization to death from any cause.
  • Secondary outcomes: The secondary outcomes were progression-free survival (PFS), which is the time from randomization to disease progression or death from any cause; objective response rate (ORR), which is the proportion of patients who had a complete or partial reduction in tumor size; disease control rate (DCR), which is the proportion of patients who had a complete or partial reduction or stabilization in tumor size; health-related quality of life (HRQoL), which is the assessment of physical, emotional, social and functional well-being; and safety and tolerability, which are the assessment of adverse events (unwanted or harmful effects) and serious adverse events (life-threatening or requiring hospitalization).

What were the main results of the trial?

The main results of the trial were:

  • Nivolumab improved overall survival compared to placebo: Nivolumab improved overall survival compared to placebo in patients with relapsed MPM. The median overall survival was 9.2 months in the nivolumab group and 6.6 months in the placebo group. The hazard ratio (HR) for death was 0.72 in favor of nivolumab, meaning that nivolumab reduced the risk of death by 28% compared to placebo. The difference was statistically significant (p=0.019), meaning that it was unlikely to be due to chance.
  • Nivolumab improved progression-free survival compared to placebo: Nivolumab improved progression-free survival compared to placebo in patients with relapsed MPM. The median progression-free survival was 3.0 months in the nivolumab group and 1.8 months in the placebo group. The hazard ratio for disease progression or death was 0.61 in favor of nivolumab, meaning that nivolumab reduced the risk of disease progression or death by 39% compared to placebo. The difference was statistically significant (p lt 00001), meaning that it was very unlikely to be due to chance.
  • Nivolumab improved objective response rate and disease control rate compared to placebo: Nivolumab improved objective response rate and disease control rate compared to placebo in patients with relapsed MPM. The objective response rate was 15% in the nivolumab group and 0% in the placebo group. The disease control rate was 44% in the nivolumab group and 27% in the placebo group. The differences were statistically significant (p lt 0.0001 and p=0.002, respectively), meaning that they were very unlikely to be due to chance.
  • Nivolumab improved health-related quality of life compared to placebo: Nivolumab improved health-related quality of life compared to placebo in patients with relapsed MPM. Health-related quality of life was measured by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), which is a questionnaire that evaluates various aspects of quality of life, such as physical, emotional, social and functional well-being, symptoms and global health status. Nivolumab improved global health status, physical functioning, role functioning, emotional functioning, social functioning, fatigue, pain, dyspnea (difficulty breathing) and appetite loss compared to placebo. The differences were statistically significant (p lt 0.05), meaning that they were unlikely to be due to chance.
  • Nivolumab was safe and tolerable compared to placebo: Nivolumab was safe and tolerable compared to placebo in patients with relapsed MPM. Adverse events were reported by 86% of patients in the nivolumab group and 81% of patients in the placebo group. Serious adverse events were reported by 25% of patients in the nivolumab group and 22% of patients in the placebo group. The most common adverse events in both groups were fatigue, nausea, diarrhea, rash and pruritus (itching). The most common serious adverse events in both groups were pneumonia, pleural effusion (fluid accumulation in the chest cavity) and dyspnea.

What are the implications of the trial?

The trial provides a new hope for patients with relapsed MPM that uses an immunotherapy drug called nivolumab to improve survival and quality of life. Nivolumab works by blocking signals that prevent the immune system from attacking cancer cells.

The trial suggests that nivolumab could be a promising treatment option for patients with relapsed MPM, as it could improve overall survival, progression-free survival, objective response rate, disease control rate and health-related quality of life compared to placebo. The trial also suggests that nivolumab could be safe and tolerable for patients with relapsed MPM, as it could cause manageable side effects.

The trial was conducted by a team of researchers from the UK and Australia. The trial was published in the journal The Lancet Oncology in 2021. The title and authors of the original article are:

Nivolumab versus placebo in patients with relapsed malignant pleural mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial by Dean A Fennell, Anna K Nowak, Sanjay Popat, Nick A Maskell, Paul Lorigan. The Lancet VOLUME 22, ISSUE 11, P1530-1540, NOVEMBER 2021 doi.org/10.1016/S1470-2045(21)00471-X