FDA Approves Ceritinib (Zykadia) for Metastatic Lung Cancer

“Earlier today the US Food and Drug Administration granted accelerated approval to ceritinib (Zykadia) for the treatment of patients with metastatic ALK-positive non–small-cell lung cancer (NSCLC). About 2% to 7% percent of NSCLC patients have ALK-positive disease.

“The new drug, a tyrosine kinase inhibitor, was approved 4 months early under the FDA’s accelerated approval program and is intended for the treatment of patients who previously received the ALK-inhibitor crizotinib.”

Editor’s note: FDA approval means that doctors can now begin prescribing ceritinib to treat patients with advanced non-small cell lung cancer (NSCLC) whose tumors have mutations in the ALK gene, as detected by molecular testing. We previously posted about ceritinib here.

New Drug Successfully Treats Crizotinib-Resistant, ALK-Positive Lung Cancer

“Although the targeted cancer treatment drug crizotinib is very effective in causing rapid regression of a particular form of lung cancer, patients’ tumors inevitably become resistant to the drug. Now a new drug called ceritinib appears to be effective against advanced ALK-positive non-small cell lung cancer (NSCLC), both in tumors that have become resistant to crizotinib and in those never treated with the older drug. The results of a phase 1 clinical trial conducted at centers in 11 countries are reported in the March 27 New England Journal of Medicine.”

Editor’s note: Crizotinib and ceritinib are meant to treat patients whose tumors have mutations in the ALK gene, as detected by molecular testing.

Phase III Study: Crizotinib Prolongs Progression-Free Survival in Previously Untreated ALK-Positive Advanced NSCLC

“In the phase III PROFILE 1014 study, the anaplastic lymphoma kinase (ALK) inhibitor crizotinib (Xalkori) was found to significantly prolong progression-free survival in previously untreated patients with ALK-positive advanced nonsquamous non–small cell lung cancer (NSCLC) compared with standard platinum-based chemotherapy.

“No unexpected safety issues were identified in the current study, and adverse events were consistent with the known safety profile for crizotinib. Efficacy and safety data from this study will be submitted for presentation at a future medical meeting.”

Editor’s note: Xalkori is a targeted therapy that is meant to treat patients whose tumors have mutations in the ALK gene, as detected by molecular testing.

EML4-ALK Fusion Testing, Targeted Crizotinib Treatment Not Cost-Effective in NSCLC

“EML4-ALK fusion testing to identify patients with advanced non–small cell lung cancer eligible for first-line, targeted treatment with crizotinib may not be cost-effective, according to study results.

“Researchers in Ontario used a Markov model to compare the cost-effectiveness of two treatment approaches for patients with stage IV nonsquamous NSCLC. One approach consisted of molecular screening and targeted treatment with crizotinib (Xalkori, Pfizer). The other approach consisted of standard care, which included platinum doublet (cisplatin and gemcitabine) as first-line therapy, second-line pemetrexed (Alimta, Eli Lilly) and third-line erlotinib (Tarceva; Genentech, Astellas Pharma).”

Editor’s Note: Molecular testing can be used to identify genetic mutations in a patient’s tumor that may point to the use of a certain treatment, personalized for him or her. This study explores the costs associated with these treatments. Of course, every patient’s treatment decisions will be made for his or her own personal reasons. You can talk to your doctor to find out if molecular testing and targeted therapies are good choices for you.

Crizotinib Beyond Progressive Disease Improved Survival in ALK-Positive NSCLC

“Patients with ALK-positive, advanced non–small cell lung cancer who received crizotinib beyond progressive disease demonstrated longer OS than patients who did not continue treatment, according to results of a retrospective study.

“The analysis included 194 patients treated with crizotinib (Xalkori, Pfizer) who experienced progressive disease defined by RECIST criteria. Of them, 120 (62%) demonstrated ongoing clinical benefit and continued treatment with crizotinib for more than 3 weeks.”

Local Radiotherapy May Allow Lung Cancer Patients to Stay on Xalkori Longer

Crizotinib (Xalkori) is effective for patients with non-small cell lung cancer (NSCLC) who have a mutation in the ALK gene, but their cancer usually develops resistance to the drug. However, this resistance may affect only part of the cancer, while the majority of the disease still responds to Xalkori. In such cases, localized radiation may be used to destroy the resistant part of the cancer (a technique dubbed ‘weeding the garden’) while patients continue to take Xalkori. In a small study, patients treated with this method could take Xalkori almost three times longer than those not eligible for the treatment. Longer times on Xalkori were associated with higher rates of 2-year survival. The average time without further relapse after the first radiation treatment was 5.5 months, and patients could be treated multiple times. Similar approaches may be effective with other targeted therapies.

Xalkori More Effective than Chemotherapy as Second-Line Treatment in ALK+ Lung Cancer

The ALK inhibitor crizotinib (Xalkori) has shown effectiveness in patients with non-small cell lung cancer (NSCLC) who have changes in the ALK gene that make the gene overactive (so-called ‘ALK-positive’ patients). A recent clinical trial compared Xalkori to chemotherapy as a second-line treatment in these patients. Over 300 patients with ALK-positive advanced NSCLC who had undergone one previous round of chemotherapy were treated either with Xalkori or one of the chemotherapy drugs pemetrexed (Alimta) or docetaxel (Taxotere). Tumors shrank in 65% of Xalkori-treated patients, compared to 20% of those receiving chemotherapy. The Xalkori-treated patients also went longer without their cancer worsening, experienced fewer symptoms, and reported higher quality of life.

Crizotinib Can Reduce Kidney Function and Testosterone Levels

A recent study suggests that crizotinib (Xalkori) can reduce kidney function. Lung cancer patients treated with Xalkori saw their kidney function decrease by 23.9% on average. Kidney function recovered when Xalkori was discontinued. However, as patients usually have to take Xalkori for months or years, these findings still warrant caution, especially in patients taking other medications that affect kidney function or with preexisting kidney damage. In an earlier study, investigators had found that Xalkori decreased testosterone levels in 84% of male patients. Because cancer drugs like Xalkori increasingly receive accelerated approval, not all of their side effects are known by the time they are approved. Doctors therefore need to carefully monitor their patients for possible adverse effects.

FDA Grants Regular Approval to Xalkori for Treatment of ALK-Mutant Lung Cancer

The U.S Food and Drug Administration (FDA) has granted regular approval to the drug crizotinib (Xalkori) for the treatment of advanced non-small cell lung cancer (NSCLC) in patients who have mutations in the ALK gene. Xalkori received accelerated approval for this application in August 2011. Regular approval was awarded based on the results of a study examining patients with advanced NSCLC whose cancer had progressed despite first-line chemotherapy. Patients treated with Xalkori went an average of 7.7 months without further cancer worsening, compared to 3.0 months in those receiving the chemotherapy agents pemetrexed (Alimta) or docetaxel (Taxotere). Tumors shrank in 65% of the Xalkori-treated patients, compared to 20% with Alimta or Taxotere. However, overall survival did not differ between the Xalkori group and the chemotherapy group.