Zykadia (ceritinib) is a tyrosine kinase inhibitor that was approved by FDA on April 29, 2014, as a medication for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib.
Lung cancer is the second most prevalent cancer found worldwide and remains the leading cause of cancer death in both men and women in the United States.1,2 Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) account for the vast majority of lung cancers identified throughout our population.2 Of those diagnosed with NSCLC, approximately 5% are known to have genetic alterations in the anaplastic lymphoma kinase (ALK) gene.3 Tumors expressing these ALK mutations are known to be highly sensitive to therapy with ALK-targeted inhibitors.3
Zykadia (ceritinib) is a tyrosine kinase inhibitor that was approved by FDA on April 29, 2014, as a medication for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib.4 Zykadia targets the inhibition of insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), ROS1, and is most active against ALK.5
It is available in a capsule strength of 150 mg.5 The dose of Zykadia is 750 mg daily on an empty stomach not to be taken within 2 hours of a meal.5 Dose adjustments for patients experiencing certain adverse effects are required and therapy should be discontinued in patients unable to tolerate 300 mg daily of the medication.5 Currently, there is no recommended dose adjustment in patients with moderate-to-severe hepatic impairment and patients utilizing concomitant strong CYP3A inhibitors may require the reduction of dose.5
Crizotinib was the first tyrosine kinase inhibitor FDA approved with antitumor activity directed toward the inhibition of ALK mutation. The recent approval of Zykadia provides an alternative agent for the management of patients expressing the mutation as well. Zykadia is known to have enhanced potency against ALK, which may play a role in future management of this patient population.6
Zykadia was granted accelerated approval based on tumor response rate and duration of response. A trial involving 163 patients with metastatic ALK-positive NSCLC who progressed on or were intolerant to crizotinib and who received 750 mg of Zykadia once daily led to the approval of the agent.5 The most common sites of metastases in the patient population studied were brain, liver, and bone.5 An overall response rate (ORR) of 54.6% (95% confidence interval [CI], 47%–62%) and a median duration of response (DOR) of 7.4 months (95% CI, 5.4–10.1 mo) was observed in this group.5 The most common adverse reactions were diarrhea, nausea, elevated transaminases, vomiting, abdominal pain, fatigue, decreased appetite, and constipation.5
FDA approval of Zykadia provides a second-line therapy that can be utilized in the treatment of ALK-positive metastatic NSCLC.5 It is approved in patients who have progressed on or are intolerant to crizotinib; however, data have shown similar efficacy in patients who were crizotinib naïve.6 This medication was given approval following a phase 1 clinical trial and thus lacks distinct information regarding the optimal dose and influence of organ dysfunction on pharmacokinetics and bioavailability.6 Furthermore, its early approval lacks extensive knowledge of adverse effects. The continued research and use of Zykadia will continue to uncover the unknown entities regarding this medication.
The estimated cost of a 70 count of 150 mg of brand name Zykadia is $7,559.80, which translates to approximately $539.99 daily for indicated dose.7
The majority of NSCLC patients who respond to crizotinib often relapse within 12 months of therapy.3 Treatment options following failure were limited to chemotherapy, palliative radiation, or supportive care.6 With FDA approval of Zykadia, another treatment option is available for management of this subgroup.
FDA approval of Zykadia will affect the manner in which we provide care to patients with ALK-positive NSCLC. This drug has the potential to possibly be used as a first-line agent in treatment of this disease state following more extensive research. Its accelerated approval may have inevitably transformed the drug development process as we know it and set the platform for the rapid approval of other medications.
Dr Moore is assistant professor, clinical and administrative sciences, Howard University College of Pharmacy, Washington, D.C.
Disclosure information: The author reports no financial disclosures as related to products discussed in this article.
1. American Lung Association. Lung cancer fact sheet. http://www.lung.org/lung-disease/lung-cancer/resources/facts-figures/lung-cancer-fact-sheet.html. Accessed July 31, 2014.
2. World Health Organization. Cancer. Updated February 2014. http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed July 31, 2014.
3. Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014;370:1189–1197.
4. FDA. FDA approves Zykadia for late-stage lung cancer. April 29, 2014. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm395299.htm. Accessed July 31, 2014.
5. Zykadia [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; April 2014.
6. Chabner BA. Approval after phase I: ceritinib runs the three-minute mile. Oncologist. 2014;19:577–578.
7. Zykadia (ceritinib). Lexi-Comp Online, Lexicomp. Hudson, OH: Lexi-Comp, Inc; July 10, 2014.