FDA Approves Keytruda Plus Pemetrexed, Platinum Chemotherapy for Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma

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The FDA has approved Merck’s Keytruda (pembrolizumab) in combination with pemetrexed and platinum chemotherapy as a first-line treatment for adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). According to the company, the regulatory action was based on promising data from the Phase II/III IND.227/KEYNOTE-483 trial, which demonstrated a 21% reduction in the risk of death (HR=0.79, p=0.0162) compared to chemotherapy alone.¹

“We’re pleased to offer a new first-line treatment option for adult patients with unresectable advanced or metastatic [MPM], a disease where prognoses are generally poor,” said Gregory Lubiniecki, MD, VP, oncology clinical research, Merck Research Laboratories, in a press release. “This milestone underscores our commitment to advancing research for patients with difficult-to-treat tumors.”

The multicenter, randomized, open-label, active-controlled IND.227/KEYNOTE-483 trial investigated the efficacy and safety of Keytruda in combination with pemetrexed and platinum chemotherapy. Investigators randomly assigned 440 patients to receive either Keytruda (200 mg) with pemetrexed (500 mg/m2 ) and cisplatin (75 mg/m2 ) or carboplatin (AUC 5-6 mg/mL/min) on day one of each 21-day cycle for up to six cycles, followed by Keytruda every three weeks, or pemetrexed (500 mg/m2 ) and cisplatin (75 mg/m2 ) or carboplatin (AUC 5-6 mg/mL/min) on day one of each 21-day cycle for up to six cycles. Treatment continued until disease progression as determined by the investigator according to modified RECIST 1.1 for mesothelioma unacceptable toxicity, or a maximum of 24 months.

Keytruda plus chemotherapy demonstrated a median overall survival (OS) rate of 17.3 months compared to 16.1 months for chemotherapy alone. Additionally, the combination significantly improved progression-free survival (PFS) versus chemotherapy alone, with a median PFS of 7.1 months. Further, the overall response rate for the combination was 52% compared to 29% with chemotherapy alone.

Adverse events (AEs) were found to be similar in both randomized groups. Common AEs associated with Keytruda included fatigue/asthenia; nausea; constipation; diarrhea; decreased appetite; rash; vomiting; cough; dyspnea; pyrexia; alopecia; peripheral neuropathy; mucosal inflammation; stomatitis; headache; weight loss; abdominal pain; arthralgia; myalgia; insomnia; palmar-plantar erythrodysesthesia; urinary tract infection; and hypothyroidism.¹

Statistics show that mesothelioma is a rare cancer in the United States, with an estimated 3,000 cases diagnosed annually. In MPM, considered to be the most common form, the five-year survival rate is 12%. Each year, around 2,500 people die as a result of mesothelioma. Symptoms can develop anywhere between 10 to 50 years after an individual has been exposed to asbestos. The average life expectancy is estimated to be from 18 to 31 months when treated.2 According to Merck, MPM can progress rapidly, and the five-year survival rate for all stages for cases diagnosed in the United States between 2014 and 2020 was 12.8%.¹

“The rate of mesotheliomas in the United States increased from the 1970s to the early 1990s, but since then it has leveled off and even gone down slightly,” reports the American Cancer Society. “These changes have largely been seen in men and are probably related to changes in workplace exposures to asbestos. The rate of mesothelioma is lower in women and has been fairly steady for some time. In many other countries, the rate of mesothelioma is still increasing.”³

References

1. FDA Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Pemetrexed and Platinum Chemotherapy as First-Line Treatment for Adult Patients With Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma (MPM). Merck. September 18, 2024. Accessed September 18, 2024. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-plus-pemetrexed-and-platinum-chemotherapy-as-first-line-treatment-for-adult-patients-with-unresectable-advanced-or-metastatic-malignant-pleu/

2. Mesothelioma Statistics. Mesothelioma.com. Accessed September 18, 2024. https://www.mesothelioma.com/mesothelioma/statistics/#:~:text=Mesothelioma%20statistics%20show%20it%20is,are%20the%20most%20common%20type.

3. Key Statistics About Malignant Mesothelioma. American Cancer Society. Accessed September 18, 2024. https://www.cancer.org/cancer/types/malignant-mesothelioma/about/key-statistics.html