The U.S. Food and Drug Administration added a warning that the entire class of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor drugs for breast cancer could cause pneumonitis. However, the regulator made it clear that the medicines’ overall benefit was still greater than the risks for advanced breast cancer patients.
The FDA said on Friday that Pfizer’s Ibrance (ingredient: palbociclib), Novartis’ Kisqali (ribociclib), and Lilly’s Verzenio (abemaciclib) might cause rare but severe lung inflammation in patients with advanced breast cancer.
CDK 4/6 inhibitors are used with hormone therapies to treat adults with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced or metastatic breast cancer. Ibrance was the first to win FDA approval in 2015.
In 2017, Kisqali and Verzenio also obtained the license and are now used around the globe.
However, the Japanese health authorities warned in May that Lilly’s Verzenio might adversely affect the lungs, causing a controversy about whether the Korean authorities should issue a safety warning, too.
Japan’s Ministry of Health, Labor and Welfare issued the safety warning, saying 14 patients treated with Verzenio developed severe lung diseases, and three of them died.
At the time, industry watchers expected that Lilly Korea might delay the market release of Verzenio, which won the regulatory nod as the second CDK 4/6 inhibitor after Ibrance.
A professor at an oncology department at a university hospital in Korea, who participated in the local trials on Ibrance, Kisqali, and Verzenio, said there was no lung issue in Korean patients.
“In Japan, many anticancer drugs, including Verzenio caused lung issues in particular. We have to check whether this problem occurred in Japan only or it became an issue because Japan has a different system of reporting adverse reactions,” he said.
It is against this backdrop that the latest FDA warning concluded that the side effect of the lung inflammation was the problem of the entire class of CDK 4/6 inhibitors.
The FDA reviewed CDK 4/6 inhibitors cases from clinical trials and post-market safety databases and found that all of the three products had reports of rare but serious adverse events and fatalities.
According to the results of the trials on the three drugs, 1 to 3 percent of patients treated with the drugs had symptoms of interstitial lung disease (ILD) and pneumonia, and less than 1 percent of the patients died. Most of the patients had no risk factor for lung disease, but certain patients had one or less.
In the safety announcement, the FDA said, “Health care professionals should monitor patients regularly for pulmonary symptoms indicative of ILD and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded.”
In patients who have new or worsening respiratory symptoms, doctors should stop the CDK 4/6 inhibitor treatment and permanently discontinue treatment in patients with severe ILD and/or pneumonitis, the FDA added.
Lilly Korea has submitted all relevant data to the Ministry of Food and Drug Safety since Japan’s safety warning on Verzenio. The Korean regulator is reviewing the submitted data. Lilly Korea requested the Health Insurance Review and Assessment Service’s grant for insurance benefit for Verzenio in July.
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