Malignant mesothelioma is an incurable and aggressive form of cancer. Though the disease’s overall prognosis is poor, researchers continue to explore treatment options to extend survival. Maintenance therapy is an additional or continuous treatment meant to maintain remission or prevent or delay the cancer’s return once it is in remission. Clinical trials of different approaches have offered mixed results.
What is Maintenance Therapy?
Maintenance therapy is a treatment that is administered to cancer patients after they have completed their primary treatment. Its goal is to prevent or delay the cancer’s return or slow the growth of advanced cancer rather than to cure it: If successful, it can extend the patient’s life.[1]
The approach taken in maintenance therapy depends on the type of cancer being treated, the patient’s condition, and the treatment they have already been provided. It may be chemotherapy, immunotherapy, radiation therapy, or hormone therapy. The determination of whether a maintenance therapy protocol is effective in treating a specific type of cancer is based on the results of clinical trials. As new drugs are introduced, they are frequently investigated for use in initial treatment and as part of maintenance therapy.[1]
There is a difference between maintenance therapy and treatments that follow or intensify the impact of a treatment with the goal of curing the cancer. The result of maintenance therapy is often unpredictable: it can last for weeks, months, or years depending on what cancer is being treated, as well as how the patient tolerates the treatment. As is true with every treatment, there is a significant risk of side effects, and pursuing maintenance therapy generally means more doctor visits and costs.[1]
Maintenance Therapy for Malignant Mesothelioma
Mesothelioma has a well-deserved reputation for being an extremely challenging and deadly form of cancer. Researchers continue to look for effective treatment protocols as well as maintenance therapy options. Clinical trials have been conducted to explore various uses for chemotherapy, as well as immunotherapy and targeted treatment options.
Studies of maintenance therapy treatments for malignant mesothelioma have included:
- A randomized Phase 2 trial conducted by researchers from HealthPartners, Inc. in Minnesota, researchers from Duke Cancer Institute, and others explored the continuation of the chemotherapy drug pemetrexed after first-line pemetrexed and platinum treatment in patients with unresectable malignant pleural mesothelioma. Half of the 49 participants were observed following primary treatment while the other half continued pemetrexed until progression.The median progression-free survival in the observation group was 3 months versus 3.4 months in the group treated with pemetrexed. Median overall survival was 11.8 months for the observation group and 16.3 months for the group treated with pemetrexed. Small percentages of patients in the group that received the maintenance therapy experienced grade 3 or 4 toxicities including anemia (8%), lymphopenia (8%), neutropenia (4%), and fatigue (4%). Though the treatment offered only a slight improvement of less than half a month in progression-free survival (PFS), it fell short of the study’s anticipated 6 months of PFS benefit among the group treated, leading the researchers to conclude that the treatment did not provide progression-free survival [2]
- In 2023, researchers from the Medical Oncology Department, National Cancer Institute of Cairo University in Cairo, Egypt, assessed the effectiveness of the chemotherapy drug gemcitabine in patients with unresectable malignant pleural mesothelioma. The selected participants had responded to 4-6 cycles of first-line chemotherapy (platinum + gemcitabine or platinum + pemetrexed). Half the group of 64 patients were treated with gemcitabine until disease progression or unacceptable toxicity and the other half received high-level supportive care. Though there was no difference in response rate to the first-line chemotherapy between the two groups, the participants that received the gemcitabine maintenance therapy experienced progression-free survival of 6.2 months, while the group provided supportive care’s progression-free survival time was just 2.8 months. Overall survival did not significantly differ between the two groups, with the first group surviving 23.3 months and the second 13.4 months.[3]
- The COMMAND Study was a Phase II randomized, double-blind, placebo-controlled, multicenter study of defactinib as maintenance therapy for malignant pleural mesothelioma that had not progressed on at least four cycles of pemetrexed/platinum therapy. Researchers recruited 344 patients with malignant pleural mesothelioma and randomized them to either receive oral defactinib or a placebo until disease progression, unacceptable toxicity, or withdrawal from the study. The median progression-free survival for the group receiving defactinib was 4.1 months compared to 4.0 months among the placebo group, and overall survival among patients who had received the placebo exceeded those who had received defactinib by almost one month. The group determined that there was no statistical difference between the groups in response rate, progression-free survival, overall survival, or quality of life, and concluded, “Defactinib cannot be recommended as maintenance therapy for advanced malignant pleural mesothelioma.”[4]
- A small multicenter study conducted by Boris Sepesi, MD of the University of Texas MD Anderson Cancer Center with Anne S. Tsao, MD as first author enrolled 28 previously untreated resectable mesothelioma patients. After extended surgical staging, the patients were treated with four cycles of cisplatin and pemetrexed plus the immunotherapy drug atezolizumab every three weeks as neoadjuvant therapy. They then had either extrapleural pneumonectomy with radiotherapy or pleurectomy/decortication. All patients received one year of maintenance therapy of atezolizumab intravenously every three weeks. The study’s goal was safety/tolerability and feasibility of this maintenance therapy approach, with safety and tolerability measured as no patient experiencing a grade 4 or 5 immune-related adverse event and feasibility being 75% of patients receiving at least one dose of maintenance therapy. Of the 28 initial patients, 25 received at least two cycles of neoadjuvant therapy, 18 underwent surgery, and 15 received atezolizumab, with three continuing the therapy at the time of the study’s report. There was no new negative safety indication from the maintenance therapy using atezolizumab.[”5”] A separate study analyzing the impact of atezolizumab as maintenance therapy following treatment for small cell lung cancer suggested that the drug provided a positive impact on overall survival.[5]
- A study conducted at the Erasmus Cancer Institute in Rotterdam, the Netherlands, tested the impact of maintenance treatment with a novel dendritic cell immunotherapyafter chemotherapy in patients with pleural mesothelioma. Over 15 months, the scientists found no improvement in overall survival compared to best supportive care alone, and a small improvement in progression-free survival. The researchers noted that patients with non-epithelioid histology fared better than those with epithelioid histology and that the treatment produced broad immune activation and a good safety profile. An editorial written by noted mesothelioma researcher Marjorie Zauderer, MD of Memorial Sloan Kettering Cancer Center accompanied the publication of the study and theorized that the study’s results may have been due to the long interval (3 months) between the last chemotherapy session and the start of maintenance therapy, during which time several patients developed progressive disease. The study authors agreed that treatment might have been more effective if given earlier.[6]
Alternatives to Maintenance Therapy for Mesothelioma
Though maintenance therapy’s goal is to prolong the time before mesothelioma tumors return or the disease progresses, the treatment is often accompanied by adverse side effects. Many patients choose to forego the treatment, choosing instead to receive supportive care or palliative care. Each represents a different approach, but they share many of the same features and goals.[7]
As described by the Multinational Association of Supportive Care, supportive care is “the prevention and management of the adverse effects of cancer and its treatment. This includes management of physical and psychological symptoms and side effects across the continuum of the cancer experience.” It encompasses rehabilitation, secondary cancer prevention, survivorship, and end-of-life care and may include judicious use of opioids and other treatments for cancer-related pain and alternative or complementary medical techniques including acupuncture. Its goal is the minimization of toxicities of cancer therapy so treatments can be continued.
By comparison, palliative care is described by the Center to Advance Palliative Care as “specialized medical care for people living with serious illnesses. It is focused on providing patients with relief from the symptoms and stress of a serious illness – whatever the diagnosis. The goal is to improve quality of life for both the patient and the family.” Palliative care is provided by physicians, nurses, and other specialists and can be offered together with curative treatment. Palliative care is not the same as hospice, which involves foregoing further disease-modifying treatment.[7]
Hospice care focuses on the patient’s quality of life as they near the end of their life. Its philosophy is based on the belief that patients should be able to live as fully and comfortably as possible for the time they have left, surrounded by their loved ones. It treats the symptoms of cancer rather than the cancer itself. It neither tries to postpone death or hasten it.
Considerations Before Choosing Maintenance Therapy for Mesothelioma
Some maintenance therapy protocols delay a cancer’s progression without prolonging survival: What this can mean is the patient experiencing a longer period without symptoms, but experiencing a more precipitous decline once the cancer begins progressing or returns.[1] With this in mind, mesothelioma patients who are offered maintenance therapy need to consider whether they are willing to bear the associated side effects of the treatment, the amount of time and effort that will be required to pursue the treatment, and the extent to which those adverse effects impact the quality of life that they have remaining.
A maintenance therapy that allows you to return to some of the daily activities you pursued before your diagnosis is different from one that offers no such improvement and is accompanied by distressing symptoms.[”] Patients are encouraged to discuss all of these issues with their mesothelioma care team, as well as with their loved ones.[8]
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