Keytruda® (pembrolizumab) for Mesothelioma Treatment

Keytruda® (pembrolizumab) is an immunotherapy drug engineered to harness a patient’s own immune system, directing it to combat and eliminate cancer cells. Keytruda, classified as an immune checkpoint inhibitor, performs this pivotal role by obstructing a specific protein on immune cells. This blockade enables the immune system to identify and obliterate cancer cells effectively.

Keytruda achieved its initial FDA approval in 2014, initially designed to address specific forms of melanoma. However, its remarkable success in clinical trials led to expanded applications. By 2016, the FDA had granted Keytruda approval for treating metastatic non-small cell lung cancer (mNSCLC). Over time, Keytruda has secured approval for over 10 distinct cancer types.

Keytruda can be prescribed for cases categorized as TMB-H (tumor mutational burden-high), wherein tumor cells exhibit a high number of genetic mutations. Remarkably, some mesothelioma tumors fall within this classification, opening the door to the potential benefits of Keytruda.

Keytruda’s Role in Mesothelioma Treatment

Keytruda operates as an immune checkpoint inhibitor, primarily targeting the immune checkpoint known as PD-1/PD-L1. This checkpoint mechanism is similar to an exclusive interaction between cancer cells (with PD-L1 protein) and T cells (a type of immune cell, with PD-1 protein). This interaction instructs T cells to ignore the cancer cells, shielding them from immune attack.

However, Keytruda’s intervention disrupts this immune checkpoint, preventing mesothelioma cancer cells from hiding. Consequently, T cells can recognize and destroy cancer cells, offering newfound hope in the battle against mesothelioma.

• Keytruda for Pleural Mesothelioma: Studies have shown that Keytruda can extend the median overall survival of pleural mesothelioma patients to approximately 18 months. When combined with other treatments, survival can be further extended. One study reported a median overall survival of nearly 24 months when Keytruda was administered alongside another form of immunotherapy for stage 3 and 4 patients who had previously undergone different treatments.
• Keytruda for Peritoneal Mesothelioma: While research on the efficacy of Keytruda for peritoneal mesothelioma is less extensive, it does indicate improved survival prospects for certain patients.
• Keytruda for Asbestos-Related Lung Cancer: Keytruda’s reach extends beyond mesothelioma, encompassing some forms of non-small cell lung cancer (NSCLC). For eligible cases, doctors may combine Keytruda with platinum and pemetrexed chemotherapy. In one study, patients with NSCLC who received chemotherapy and Keytruda achieved a median survival of 22 months, more than doubling their survival compared to chemotherapy alone.

Keytruda Treatment Process

Keytruda is administered intravenously (IV), with each IV infusion typically lasting around 30 minutes. These infusions are repeated every three weeks, with courses of treatment extending up to two years or even longer if deemed effective and well-tolerated.

It is important to note that Keytruda is employed as a second-line treatment for mesothelioma patients whose disease either did not respond to initial treatment or recurred following surgery, radiation, or chemotherapy. This approach has shown promise in multiple clinical trials.

Survival with Keytruda

Numerous clinical studies have explored the impact of Keytruda on mesothelioma survival rates. The median survival duration for pleural mesothelioma patients undergoing Keytruda treatment usually falls within the range of 10 to 18 months.

The KEYNOTE-028 clinical trial, conducted across 13 sites in six countries, yielded promising results. This study, one of the earliest to examine the efficacy of Keytruda in treating malignant pleural mesothelioma, reported several significant findings:

• 56% of patients experienced a reduction in tumor size.
• Patients enjoyed approximately five months without tumor progression.
• Median overall survival reached an impressive 18 months.

This median survival result stands among the best reported for second-line mesothelioma therapy, igniting further interest in exploring the potential of Keytruda.

Keytruda and CAR T-Cell Therapy

Another study combined Keytruda with CAR T-cell therapy, a groundbreaking approach to cancer treatment. CAR T cells, generated from a patient’s immune cells, have the unique ability to identify and attack cancer cells.

Participants in this study had already undergone at least one prior mesothelioma treatment. After CAR T-cell therapy, they received Keytruda. The combination demonstrated remarkable results, with patients experiencing a median survival of 23.9 months. Significantly, over 70% of these patients were in the late stages of mesothelioma, where life expectancy typically ranges from 12 to 16 months. This suggests that CAR T cells and Keytruda may have extended survival by a year for these patients.

Keytruda Research Continues

The effectiveness of Keytruda in mesothelioma treatment continues to be explored through various ongoing studies. Several active mesothelioma clinical trials incorporate Keytruda as part of their treatment strategy, with the hope of achieving breakthroughs in the quest for a mesothelioma cure.

Side Effects of Keytruda

Keytruda’s side effects are typically mild, although common. In the KEYNOTE-028 trial, 64% of mesothelioma patients receiving Keytruda reported at least one side effect. Nausea and fatigue were the most frequently reported side effects, affecting 24% of patients. Other common side effects encompassed joint stiffness, itching, decreased appetite, and dry mouth. Importantly, no study participants discontinued treatment due to severe side effects.

Although the majority of side effects appear to be mild in pleural mesothelioma patients undergoing Keytruda treatment, individuals with different types of cancer have encountered more severe responses. In certain instances, Keytruda has led to immune-mediated responses or autoimmune reactions, where the immune system may mistakenly attack healthy tissues or induce other complications. While these reactions are considered uncommon, they may resolve after discontinuing treatment.

Eligibility for Keytruda

Keytruda’s FDA approval pertains to patients with TMB-H classified tumors. To be eligible for Keytruda treatment, mesothelioma patients should meet certain criteria:

• The patient’s case is deemed inoperable.
• No other satisfactory treatment options are available.
• The patient’s tumor falls within the TMB-H category, signifying a high number of genetic mutations.
• The patient’s cancer has either not responded to previous treatment or has recurred despite prior treatment.

It’s important to note that Keytruda has not received specific FDA approval for mesothelioma, but its potential role is acknowledged by experts. Organizations like the National Comprehensive Cancer Network (NCCN) include Keytruda in their treatment guidelines, suggesting it as a potential second-line treatment for pleural mesothelioma.

Any mesothelioma patient considering Keytruda should engage in a comprehensive discussion with their oncologist. These experts can provide invaluable insights into the potential benefits and risks of available therapies, helping patients make informed decisions tailored to their unique circumstances.