February 1, 2019 - FDA Approvals, News & Updates

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FDA Resumes Operations After Government Shutdown Ends

On Saturday, January 26, 2019, the US Food and Drug Administration (FDA) issued a statement advising all employees to return to work on their next scheduled duty day following the lifting of the government shutdown. The result of a political impasse, the shutdown had been ordered by President Trump’s administration on December 21, 2018. For the duration of the 35-day interruption, many routine FDA functions came to a halt, including the testing of new drugs and approving new indications of previously approved drugs. The effect of the shutdown on the forecasted schedule for the first quarter of 2019 remains to be seen, although analysts were anticipating some lag time because of a backlog that mounted while the FDA faced a steep reduction in personnel and funding during the government action.

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FDA Approves New Drug Indication for Use in Hepatocellular Carcinoma

Despite the government shutdown, an expected approval did occur. On January 14, 2019, the FDA approved cabozantinib (Cabometyx; Exelixis) for use in hepatocellular carcinoma (HCC) previously treated with sorafenib (Nexavar). HCC is the most common form of liver cancer and is the fastest-rising cause of cancer-related death in the United States.1,2

The new indication for cabozantinib was based on CELESTIAL, a randomized (2:1), double-blind, placebo-controlled, multicenter phase 3 trial in patients with HCC who had previously received sorafenib and had Child Pugh Class A liver impairment.

Patients in this trial were randomized to receive cabozantinib 60 mg orally once daily (n = 470) or placebo (n = 237) until disease progression or unacceptable toxicity.

Median overall survival was 10.2 months (95% confidence interval [CI], 9.1-12.0) for patients receiving cabozantinib and 8 months (95% CI, 6.8-9.4) for those receiving placebo (hazard ratio [HR], 0.76; 95% CI, 0.63-0.92; P = .0049); additional outcome measures were progression-free survival (PFS) and overall response rate (ORR), as assessed by investigators per RECIST 1.1. Median PFS was 5.2 months (range, 4.0-5.5) and 1.9 months (range, 1.9-1.9) in the cabozantinib and placebo arms, respectively (HR, 0.44; 95% CI, 0.36-0.52; P <.001). ORR was 4% (95% CI, 2.3-6.0) in the cabozantinib arm and 0.4% (95% CI, 0.0-2.3) in the placebo arm.

“Patients with this form of advanced liver cancer have few treatment options, particularly once their disease progresses following treatment with sorafenib […] and the results of the CELESTIAL trial demonstrate that Cabometyx has the efficacy and safety profile to become an important new therapy in our efforts to slow disease progression and improve treatment outcomes,” said Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center, New York, lead investigator on CELESTIAL, in a press release for the manufacturer.

The recommended cabozantinib dose is 60 mg orally, once daily at least 1 hour before, or 2 hours after eating. The most common adverse reactions in ≥25% of patients who received cabozantinib in clinical trials were diarrhea, fatigue, decreased appetite, palmar-plantar erythrodysesthesia, nausea, hypertension, and vomiting.

  1. International Agency for Research on Cancer. GLOBOCAN 2018. Liver Fact Sheet. http://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf. Accessed January 2019.
  2. American Cancer Society: Cancer Facts and Figures 2019. www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf. Accessed January 2019.

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FDA Approves Pembrolizumab for Merkel-Cell Carcinoma

On December 19, 2018, the FDA granted accelerated approval to pembrolizumab (Keytruda; Merck) for adult and pediatric patients with recurrent locally advanced or metastatic Merkel-cell carcinoma (MCC). This indication is approved based on tumor response rate and durability of response.

The prevalence of MCC is on the rise in the United States and is expected to continue to increase. It usually arises as a nondescript, painless red or purple bump on UV-exposed skin and is often misdiagnosed as a cyst. MCC grows rapidly and has a high propensity for metastasis. It is most frequently diagnosed in individuals aged >50 years and in those with systematic immunosuppression.

The approval was based on data from the Cancer Immunotherapy Trials Network (CITN)’s CITN-09/KEYNOTE-017 trial. The phase 2, nonrandomized, multicenter, open-label trial enrolled 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy. Patients received pembrolizumab 2 mg/kg every 3 weeks until unacceptable toxicity or disease progression.

The recommended pembrolizumab dose for MCC is 200 mg administered as a 30-minute intravenous infusion every 3 weeks for adults; 2 mg/kg (to a maximum of 200 mg) administered as a 30-minute intravenous infusion every 3 weeks for patients aged <18 years (pediatric patients).

The most frequently reported adverse reactions of pembrolizumab were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.

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Last modified: February 20, 2019