On 10 August 2021, the US Food and Drug Administration (FDA) approved the combination of lenvatinib (Lenvima, Eisai) plus pembrolizumab (Keytruda, Merck) for first-line treatment of adult patients with advanced renal cell carcinoma (RCC).<\/p>\n
The efficacy of this combination was investigated in CLEAR (Study 307\/KEYNOTE-581; NCT02811861), a multicentre, open-label, randomised phase III study in patients with advanced RCC in the first-line setting. Patients were enrolled regardless of PD-L1 tumour expression status. The efficacy population supporting this approval included patients randomised to lenvatinib plus pembrolizumab (n=355) compared with those randomised to single-agent sunitinib (n=357).<\/p>\n
Progression-free survival (PFS), assessed by independent radiologic review according to RECIST v1.1, and overall survival (OS) were the major efficacy endpoints.<\/p>\n
Patients receiving pembrolizumab with lenvatinib had a median PFS of 23.9 months (95% confidence interval [CI] 20.8, 27.7) compared with 9.2 months (95% CI 6.0, 11.0) for those receiving sunitinib (hazard ratio [HR] 0.39; 95% CI 0.32, 0.49; p < 0.0001).<\/p>\n
Median OS was not reached in either arm (HR 0.66; 95% CI 0.49, 0.88; p = 0.0049).<\/p>\n
The objective response rates were 71% (95% CI 66, 76) and 36% (95% CI 31, 41; p < 0.0001); complete response rates were 16% and 4% on the combination and sunitinib arms, respectively.<\/p>\n
The most common adverse reactions reported in \u226520% of patients who received lenvatinib and pembrolizumab in clinical studies are fatigue, diarrhoea, musculoskeletal pain, hypothyroidism, hypertension, stomatitis, decreased appetite, rash, nausea, decreased weight, dysphonia, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, haemorrhagic events, vomiting, constipation, hepatotoxicity, headache, and acute kidney injury. Arterial thrombotic events occurred in 5% of patients in CLEAR, including myocardial infarction (3.4%) and cerebrovascular accident (2.3%).<\/p>\n
The recommended dosages for patients with advanced RCC are lenvatinib 20 mg orally once daily with pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks or 400 mg administered as an intravenous infusion over 30 minutes every 6 weeks up to 2 years, until disease progression or until unacceptable toxicity.<\/p>\n
Full prescribing information for Lenvima is available here<\/a> and for Keytruda here<\/a>.<\/p>\n This review used the Real-Time Oncology Review<\/a> pilot programme, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment. The FDA approved this application approximately 1 month ahead of the FDA goal date.<\/p>\n This application was granted priority review and breakthrough therapy designation for this indication.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n