Mesothelioma Clinical Trial Studies Keytruda, Lenvatinib Combination

Research & Clinical Trials

A possible second-line treatment for pleural mesothelioma may be on the horizon after a phase II clinical trial showed impressive efficacy with early returns from the Netherlands Cancer Institute in Amsterdam.

The single-arm, open-label clinical trial involved the combination of pembrolizumab, an immunotherapy drug known by the brand name Keytruda, in combination with lenvatinib. Synergy between the two cancer drugs was impressive.

Results of the clinical trial were presented earlier this week at the IASCL 2022 World Conference on Lung Cancer in Vienna, Austria.

“We are really pleased with the combination,” co-investigator Li-Anne Douma, who made the presentation, told The Mesothelioma Center at “The results thus far were far better than expected.”

Early Results Show Survival Benefits

The trial involved 38 patients whose unresectable mesothelioma had begun progressing after standard-of-care chemotherapy. They enrolled between March 5, 2021, and Jan. 31, 2022.

Each received Keytruda intravenously every three weeks and lenvatinib orally once a day. They remained on treatment until unacceptable toxicity or disease progression. Many are still being treated.

Early results cited in the presentation included a median overall survival rate of 11.4 months and a median progression-free survival rate of 5.7 months, although Douma cautioned that those numbers were preliminary and only a rough estimation. 

“I would like to avoid conclusions being drawn too early,” she said.

Lenvatinib Can Block Tumor Growth

Although success with Keytruda has been celebrated with some cancers, its response rate as a monotherapy has been only 20% with mesothelioma, accentuating the need to find an effective drug partner to provide the needed synergy.

The objective response rate of the Keytruda/lenvatinib combination was an impressive 58%.

In 2020, the U.S. Food and Drug Administration approved the use of Keytruda for certain metastatic tumors, including certain cases of mesothelioma, but the search for an effective combination continues.

Lenvatinib has shown it can block tumor growth by targeting specific proteins Keytruda can’t reach. It has been effective with only select cancers and is known as precision medicine.

The drug, which is already FDA approved, has been used successfully with Keytruda for the treatment of endometrial cancer. Lenvatinib is prescribed alone to treat hepatocellular carcinoma, a type of liver cancer. It is used in other combinations to help treat renal cell carcinoma.

Searching for Second-Line Mesothelioma Treatments 

The need for second-line treatments of unresectable mesothelioma is ongoing. The average life expectancy of someone with the disease is 12 to 21 months.

Pleural mesothelioma is a rare cancer caused mostly by long-ago inhalation or ingestion of asbestos fibers. It is diagnosed in an estimated 3,000 people annually in the U.S.

The FDA approved the immunotherapy combination of Opdivo and Yervoy in 2020 for first-line treatment, adding to standard-of-care chemotherapy. Neither treatment, though, has shown an ability to be effective long-term for most patients.

“Despite many trials and a list of recommendations, there is still no standard treatment in the second line,” Douma said. “The need to find a standard treatment is high.”

She said this latest trial combination could potentially fill the void, but that larger trials are needed. 

The median age in Douma’s trial was 70.5 years, and 89.5% of the patients had epithelioid mesothelioma, the most treatable type of mesothelioma. 

Ten of the 38 patients reported treatment-related side effects that ranged from serious to minor. They included hypertension, hoarseness, fatigue, diarrhea and anorexia. Dose reductions or discontinuation of lenvatinib were required by 76% of the trial participants.

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