Xalkori (crizotinib), a lung cancer drug that was approved in 2011 under the Food and Drug Administration's accelerated approval, has passed the last hurdle to regular approval. On Nov. 20, the FDA gave the ruling after a phase 3 clinical study confirmed that the drug works in patients who have metastatic cancer with a particular genetic mutation called ALK and who had progressed on platinum-based chemotherapy. Specifically, Xalkori works in lung cancers that are driven by a mutation in the anaplastic lymphoma kinase (ALK) gene, which occurs in about 5 percent of non-small cell lung cancers. Accelerated approval is a conditional approval the FDA grants for drugs that show a significant improvement before a trial is completed. It can be based on survival, delayed disease progression or another endpoint that was pre-determined before the trial began. Efficacy of the drug must be verified in a later study, either a phase 3 or 4 trial before it can be given a regular approval.Previous results, which led to the accelerated approval, were based on two single-arm studies, meaning all patients in the study received the investigational drug rather than being randomly assigned to receive the investigational drug or a standard of care. These studies showed Xalkori improved objective response rates, meaning the tumors shrunk with Xalkori in 50 percent and 61 percent of the time in the two studies, respectively.[Xalkori approved for non-small cell lung cancer – Sept 1, 2011] This new approval is based on results that showed the drug delayed disease progression for 7.7 months compared to chemotherapy, which only kept the cancer from growing for 3 months. Side effects included vomiting, diarrhea, constipation, fatigue and vision impairments. Many accelerated approvals later receive regular approval. A paper examining accelerated approvals and post-marketing studies found that from Dec. 11, 1992 to July 1, 2010, the FDA granted 35 oncology products accelerated approval, which accounted for 47 new indications. Clinical benefit was later confirmed in subsequent studies for 26 of the 47 new indications. The average time between accelerated approval and regular approval was more than four years, but ranged anywhere from less than a year to more than 12 years. During that time, three indications were revoked or had a restricted distribution due to follow-up studies. To better understand this newest approval for Xalkori, we asked the FDA a few questions:1. What is the significance of the regular approval for Xalkori? • Xalkori received a broad indication for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) in 2011 because this magnitude of high response rates had not been observed with standard approved treatments for lung cancer. Because of this, we didn't want to require patients to progress on chemotherapy before enabling access to a drug that appeared to provide a significant benefit over the standard of care. Xalkori's accelerated approval in 2011 was based on response rates in single-arm trials, and its regular approval is based on a post-marketing trial that provides confirmation of the clinical benefit based on a randomized study against chemotherapy. 2. What does it mean to patients?• Xalkori's regular approval highlights an evolving paradigm of very rapid drug development, where we are able to get drugs to the patients who need them most at an accelerated pace. Practically speaking for NSCLC patients, Xalkori's regular approval gives access to a therapy that demonstrates superior progression-free survival by about five months and a reduction in the relative risk of progression by about 50 percent. The post-marketing trial provided supporting evidence of higher response rates – 65 percent of tumors shrunk versus 20 percent in those receiving chemotherapy. The randomized trial also provided additional safety data, which helped the FDA determine that its risk-benefit was acceptable. You can read more about the regular approval at fda.gov. You can also read more about accelerated approval and other routes to FDA approval in CURE's article "A Primer on How Faster Approval Works." We'll be featuring advancements in lung cancer in an upcoming issue of CURE, so stay tuned for more updates.