ASCO 2014 Lung Cancer Roundup


Every year, thousands of people gather in Chicago, Illinois, for the American Society of Clinical Oncology (ASCO) Annual Meeting. The largest meeting of its kind, ASCO brings together doctors, researchers, nurses, patient advocates, pharmaceutical company representatives, and more to discuss the latest in cancer research. Here are some of the most exciting new developments in lung cancer research presented last week at ASCO 2014: Continue reading…


Responses with Crizotinib in MET-Amplified Lung Cancer Show New Targetable Form of Disease

In 2011, the drug crizotinib earned accelerated approval by the US FDA to target the subset of advanced non-small cell lung cancers caused by rearrangements of the anaplastic lymphoma kinase (ALK) gene, and subsequently was granted regular approval in 2013. The drug also has shown dramatic responses in patients whose lung cancers harbored a different molecular abnormality, namely ROS1 gene rearrangements. Previously unreported phase 1 clinical trial results now show that crizotinib may have a third important molecular target. In advanced non-small cell lung cancer patients with intermediate and high amplifications of the MET gene, crizotinib produced either disease stabilization or tumor response. Sixty-seven percent of patients with high MET amplification showed prolonged response to the drug, which lasted from approximately 6 months to nearly 2.5 years.”

Editor’s note: Crizotinib (aka Xalkori) is a targeted therapy drug that kills cancer cells by targeting certain molecules found in the cells. It was already known that crizotinib works well for some patients with advanced non-small cell lung cancer (NSCLC) whose cancer cells have mutations in the ALK gene and in the ROS1 gene; such mutations, or “molecular biomarkers,” are detected by a medical procedure known as “molecular testing,” or “genetic testing.” Now, scientists say that crizotinib may also be effective for patients with advanced NSCLC whose tumors have abnormally high activity of a protein called MET, which can also be detected via molecular testing.


Thwarting Drug Resistance in Lung Cancer


If you’ve read up on lung cancer research in the last few years, you probably know that large strides have been made in targeted therapies for non-small cell lung cancer (NSCLC). Targeted therapies are drugs that identify and attack specific mutated proteins that are detected in tumors. Because noncancerous cells do not have these specific mutations, targeted therapies can make a beeline for cancer, while leaving healthy tissue unharmed. Continue reading…


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.


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.