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FDA Grants Priority Review to Keytruda Combination as a First-Line Treatment for Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma


Priority review designation for Keytruda is based on promising results from the Phase II/III IND.227/KEYNOTE-483 trial, which demonstrated improved overall survival in patients with unresectable advanced or metastatic malignant pleural mesothelioma.

Asbestos. Image Credit: Adobe Stock Images/BillionPhotos.com

Image Credit: Adobe Stock Images/BillionPhotos.com

Merck has announced that the FDA granted Priority Review designation to its application for Keytruda (pembrolizumab) plus chemotherapy as a first-line treatment for patients with unresectable advanced or metastatic malignant pleural mesothelioma. According to the company, the application was a based on positive data from the Phase II/III IND.227/KEYNOTE-483 trial, which found that Keytruda in combination with chemotherapy significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared to chemotherapy alone. Further, death was reduced by 21% (HR=0.79 [95% CI, 0.64-0.98]; two-sided p value=0.0324), with a median OS of 17.3 months (95% CI, 14.4-21.3) versus 16.1 months (95% CI, 13.1-18.2) for chemotherapy alone. After a year of treatment, the estimated PFS rate was 26% for the combination of chemotherapy and Keytruda.

The randomized, open-label IND.227/KEYNOTE-483 trial’s primary endpoint was OS, with secondary endpoints that included PFS and ORR. The investigators randomly assigned 440 patients to receive either Keytruda (200 mg intravenously [IV] every three weeks [Q3W] for up to 35 cycles) plus pemetrexed (500 mg/m2 Q3W for six cycles) and cisplatin (75 mg/m2 Q3W for six cycles; carboplatin substitution, or pemetrexed and cisplatin.1

“Malignant pleural mesothelioma is typically diagnosed in advanced stages when curative surgery is not an option, and progresses quickly,” said Gregory Lubiniecki, MD, VP, oncology clinical research, Merck Research Laboratories, in a press release. “We continue to evaluate Keytruda in new and difficult-to-treat tumors and look forward to working with the FDA to help bring Keytruda as a potential treatment option to certain patients with advanced malignant pleural mesothelioma.”

According to the American Cancer Society, mesothelioma is extremely rare in the United States, with an estimated 3,000 cases diagnosed on a yearly basis. After rising consistently from the 1970s to the early 1990s, rates have slightly decreased in recent years. These changes can be credited to changes in workplace exposures to asbestos; however, the rate of mesothelioma is increasing in numerous countries.2

“During 1999–2015, a total of 45,221 malignant mesothelioma deaths were reported, increasing from 2,479 (1999) to 2,597 (2015). Mesothelioma deaths increased for persons aged ≥85 years, for both sexes, persons of white, black and Asian or Pacific Islander race, and all ethnic groups. Continuing occurrence of malignant mesothelioma deaths in persons aged <55 years suggests ongoing inhalation exposure to asbestos fibers and possibly other causative EMPs,” reported the authors of a study on mesothelioma mortality for the Centers for Disease Control and Prevention. “Despite regulatory actions and decline in asbestos use, the annual number of malignant mesothelioma deaths remains substantial. Contrary to past projections, the number of malignant mesothelioma deaths has been increasing. The continuing occurrence of mesothelioma deaths, particularly among younger populations, underscores the need for maintaining efforts to prevent exposure and for ongoing surveillance to monitor temporal trends.”3


1. FDA Grants Priority Review to Merck’s Application for KEYTRUDA® (pembrolizumab) Plus Chemotherapy as First-Line Treatment of Patients With Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma. Merck. May 29, 2024. Accessed May 29, 2024. https://www.merck.com/news/fda-grants-priority-review-to-mercks-application-for-keytruda-pembrolizumab-plus-chemotherapy-as-first-line-treatment-of-patients-with-unresectable-advanced-or-metastatic-malignant-pl/

2. Key Statistics About Malignant Mesothelioma. American Cancer Society. Accessed May 29, 2024. https://www.cancer.org/cancer/types/malignant-mesothelioma/about/key-statistics.html

3. Malignant Mesothelioma Mortality — United States, 1999–2015. CDC. March 3, 2017. Accessed May 29, 2024. https://www.cdc.gov/mmwr/volumes/66/wr/mm6608a3.htm

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