FDA Approves Pembrolizumab Plus Pemetrexed and Platinum Chemotherapy for Malignant Pleural Mesothelioma
The approval is based on positive results from the phase 2/3 IND.227/KEYNOTE-483 trial.
Pembrolizumab (Keytruda; Merck) plus pemetrexed (Alimta; LillyMedical) and platinum chemotherapy in the first line received FDA approval for the treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). According to data from the phase 2/3 IND.227/KEYNOTE-483 trial (NCT02784171), the combination treatment achieved a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) versus chemotherapy alone.1
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Mesothelioma is a rare type of cancer characterized by the growth of tumors in the mesothelium, the tissue that covers the lungs, heart, and reproductive organs. According to the American Cancer Society, about 3000 new cases are diagnosed each year, which predominantly affects older individuals. MPM is the most common form of mesothelioma that develops in the lining of the lungs and accounts for about 75% of all cases. MPM can progress rapidly, and patients typically have a 5-year survival rate in any stage of the disease.2,3
Treatment for MPM can be difficult due to the spread of tumor masses across tissues and potential risk to nearby nerves and blood vessels. Patients are commonly treated with radiation therapy, chemotherapy, and surgery; however, these treatments may not effectively clear all the tumor growth, calling for advanced treatments with more targeted capabilities. The approval of the combination treatment pembrolizumab plus pemetrexed and platinum chemotherapy may provide patients with the multi-faceted approach needed to treat MPM.4
Pembrolizumab is an anti-programmed death receptor-1 (PD-1) monoclonal antibody that blocks PD-1 to activate T lymphocytes, which help fight tumor cells. In the phase 2/3 IND.227/KEYNOTE-483 (NCT02784171) trial, researchers evaluated the efficacy and safety of pembrolizumab when used in combination with pemetrexed and platinum chemotherapy. Their study enrolled 440 patients with unresectable advanced or metastatic MPM and no prior lines of treatment who were randomized (1:1) to one of the following treatment arms: pembrolizumab (200 mg) with pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) or carboplatin (AUC 5-6 mg/mL/min) on day 1 of each 21-day cycle for up to 6 cycles, followed by pembrolizumab every 3 weeks; or pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) or carboplatin (AUC 5-6 mg/mL/min) on day 1 of each 21-day cycle for up to 6 cycles.3
According to the data, the combination treatment including pembrolizumab demonstrated a median OS of 17.3 months (95% CI, 14.4-21.3) compared with 16.1 months (95% CI, 13.1-18.2) for chemotherapy alone. There was an observed improvement in PFS (HR=0.80 [95% CI, 0.65-0.99], p=0.0194; median PFS 7.1 months [95% CI, 6.9-8.1]) and reduction in risk of death by 21% (HR=0.79 [95% CI, 0.64-0.98]; p=0.0162). Additionally, the pembrolizumab treatment arm had a higher overall response rate compared with chemotherapy (52% [95% CI, 45.5-59.0] versus 29% [95% CI, 23.0-35.4], respectively; P<.00001).3
The clinical findings and approval of pembrolizumab plus pemetrexed and platinum chemotherapy have significant implications for the future treatment of patients with MPM. With a multi-faceted, targeted approach, clinicians may be able to more effectively treat and clear tumors in harder to reach places.
“We’re pleased to offer a new first-line treatment option for adult patients with unresectable advanced or metastatic malignant pleural mesothelioma, a disease where prognoses are generally poor,” Gregory Lubiniecki, MD, vice president of oncology clinical research at Merck Research Laboratories, said in a news release. “This milestone underscores our commitment to advancing research for patients with difficult-to-treat tumors.”2
