Keytruda Plus Chemo New Standard of Care in Pleural Mesothelioma

It's necessary for patients with pleural mesothelioma to explain all symptoms of side effects to their doctors.

Until recently, the treatment landscape for patients with advanced or metastatic pleural mesothelioma was chemotherapy, an expert told CURE®. However, a recent Food and Drug Administration (FDA) approval introduced Keytruda (pembrolizumab) plus chemotherapy as a new first-line treatment option.

Of note, Keytruda is a type of immune checkpoint inhibitor (immunotherapy) and monoclonal antibody. The drug helps the immune cells destroy cancer cells, according to the National Cancer Institute.

“The ability of using chemo plus immunotherapy just gives us an additional option for patients who we see in the office,” Dr. Hossein Borghaei told CURE® during an interview. “At this point, I think it’s pretty well-established that chemo alone is no longer the standard of care. But that’s how the landscape has changed recently.”

Borghaei is the chief of the Division of Thoracic Medical Oncology and a professor in the Department of Hematology/Oncology at Fox Chase Cancer Center in Philadelphia.

Treatments and combinations depend on the subtype of mesothelioma, Borghaei explained. Patients with non-epithelioid mesothelioma responded “much better” to immunotherapy than patients with the epithelioid subtype, although immunotherapy was still beneficial to those with the epithelioid subtype.

The Importance of Keytruda Plus Chemo in Pleural Mesothelioma

Not only does the FDA approval of Keytruda plus chemotherapy offer a new treatment option in the first line, but it also changed the standard of care, Borghaei said.

“[The FDA approval] represents an improvement in what we have been doing, above and beyond just chemotherapy,” he noted. “The goal has always been, obviously, to find better and more effective treatments for our patient population.”

He explained that standard of care treatments may change based on positive findings from phase 3 trials. When a phase 3 trial compares standard of care to a new treatment and the new treatment is more effective and safer in the patient population, then it can be considered as a new standard of care.

Data from the phase 3 KEYNOTE-483 trial, which led to the approval of Keytruda plus chemotherapy, demonstrated statistically significant improvements in overall survival (time patients live, regardless of their disease status).

“[This study] suggests that the addition of immunotherapy can, in fact, improve overall survival and the three-year overall survival rate in this patient population,” Borghaei added. “It is a regimen that we consider, for the most part, to be tolerable for the majority of our patients. Because the combination improved overall survival, we consider this to be a better standard than just chemotherapy.”

Unmet Needs that Persist in Treatment for Pleural Mesothelioma

The step forward towards a newer and more effective standard of care has been made by this FDA approval. Nevertheless, there are still unmet needs for the wider patient population, Borghaei explained.

“Unfortunately, not everybody responds to any of these regimens. We can’t say that 100% of patients with mesothelioma are going to benefit, so we definitely need additional treatment options for patients who might not benefit from chemotherapy and immunotherapy,” he said.

Of note, the FDA approved Keytruda plus chemotherapy as first-line treatment. Borghaei emphasized that second-line treatments for patients who experience disease progression (worsening or spreading) are currently “not very well defined.”

LEARN MORE: Differences Between Lung Cancer and Pleural Mesothelioma

Side Effects Associated With Keytruda Plus Chemotherapy

Among patients with pleural mesothelioma receiving Keytruda plus chemotherapy as first-line treatment, the side effects were consistent with patients who have different cancer types, such as lung cancer, Borghaei explained.

Treatment with immunotherapy may lead to inflammatory conditions and effects on the skin, he said. Common side effects associated with chemotherapy included decreased blood counts and effects on the kidneys and liver.

As general advice, Borghaei recommended patients with mesothelioma have a consultation with medical oncologists who work closely with mesothelioma and are familiar with the treatment options.

“Don’t ignore symptoms,” he said. “There has to be that open communication. Many of my patients say, ‘Well, I didn’t call because I didn’t want to bother you.’ But it’s not that they’re bothering me — they’ve never had chemo or immunotherapy. They don’t know how they’re supposed to feel, so the sooner I know, the better I can manage [the symptoms and side effects].

“Not being shy about calling and saying [that you] have symptoms is always a good idea.”

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