The FDA also warned that crizotinib has been associated with potentially life-threatening pneumonitis (4 of 255 patients; 1.6%); the drug should be stopped permanently in patients with treatment-related pneumonitis, the agency said. Pregnancy is also a contraindication.
Consideration of crizotinib was expedited under the FDA’s priority review program for drugs with the potential to provide major advances in diseases for which no effective therapy exists. No survival data were reported, and the agency granted accelerated approval based on the objective response rates being reasonably likely to predict clinical benefit. Confirmatory trials are required.
Pfizer is already conducting two randomized, open-label, postmarketing phase III studies: one comparing the safety and efficacy of crizotinib with standard of care chemotherapy (pemetrexed [Alimta] or docetaxel [Taxotere]) in patients with previously treated, advanced, ALK-positive NSCLC, and the other comparing efficacy and safety of the agent to pemetrexed/cisplatin or pemetrexed/carboplatin in previously untreated patients with advanced, ALK-positive, nonsquamous NSCLC, according to a Pfizer statement.
Dr. Kris predicted that the addition of the required ALK fusion diagnostic test – at a cost of $250 – won’t be a large burden. "I think it will be very quick to add ALK testing as part of that," he said, noting the ASCO and NCCN recommendations for EGFR testing.
Because the fusion gene has been seen in patients with lung tumors other than adenocarcinomas, testing should ideally be done in all lung cancer patients, Dr. Kris added. "Based on broader experience with EGFR mutations, I think we’ve learned that there is no clinical profile that comes anywhere near the accuracy of the testing. ... I would caution against any particular kind of profile that would make one select who to test and who not to test," he said.
Recommended dosing is 250 mg taken orally twice daily with or without food. In some patients, a dosing interruption and/or dose reduction to 200 mg taken orally twice daily may be required; if further reduction is necessary, the label recommends 250 mg taken orally once daily.
Monthly treatment with crizotinib will cost $9,600. And because the tumor is driven by the mutation, the treatment is indefinite. Several patients from the trials have now been taking the drug for more than a year. "There is no stop time as long as they’re benefiting," said Dr. Mace Rothenberg, Pfizer senior vice president of clinical development and medical affairs in the oncology business unit.
Pfizer has two financial assistance programs for patients. The Pfizer First Resource Program connects eligible insured patients to specialty pharmacies to get reimbursement-support services and to obtain the medications. For uninsured and underinsured patients, the program will provide eligible patients with free medication. There is also a copay assistance program for eligible privately insured patients. Information about eligibility can be obtained by calling First Resource (1-877-744-5675), or by visiting XALKORI.com.
Dr. Kris is a consultant for Pfizer. Dr. Bunn has served as a consultant or on an advisory board for several companies in the past 2 years, but noted that he received no funding for any press discussions or research on crizotinib and has no Pfizer stock.