NIH Announces the Launch of 3 Integrated Precision Medicine Trials; ALCHEMIST is for Patients with Certain Types of Early-Stage Lung Cancer

Editor’s note: Oncologists sometimes treat late-stage lung cancer patients based on the results of molecular tumor tests, which can reveal genetic mutations that cause tumor growth. This story is about a new study launched to find early stage lung cancer patients whose tumors have mutations in the EGFR or ALK genes. The study will explore whether drugs targeted against those genes will improve survival for the patients.

“The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials, or ALCHEMIST, was launched today to identify early-stage lung cancer patients with tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against those changes can lead to improved survival.

“ ‘We believe that the findings from ALCHEMIST will not only help answer an important question about the addition of targeted therapies in earlier stage disease but will also help us in understanding the prevalence and natural history of these genomic changes in earlier stage lung cancer. We also hope to gain a better understanding as well regarding the genetic changes in the tumor at the time of recurrence,’ said Shakun Malik, M.D., head of Thoracic Cancer Therapeutics in the Clinical Investigations Branch of the National Cancer Institute (NCI). ‘The findings will help to define clinical, biologic and molecular behaviors of this type of lung cancer.’ “


Drugs to Avoid in Patients on Tyrosine Kinase Inhibitors

Editor’s note: More and more people with cancer are being treated with drugs known as tyrosine kinase inhibitors (TKIs). As with any other drug, oncologists who prescribe TKIs must be aware of other drugs a patient is taking to ensure there will not be a dangerous drug-drug interaction. Researchers recently published a report outlining known and potential drug-drug interactions between TKIs and other drugs. Oncologists and patients may wish to take these into account when considering cancer treatment with TKIs.

“With the rapid and widespread uptake of tyrosine kinase inhibitors (TKIs) in oncology over the past several years, serious drug–drug interactions are an “increasing risk,” according a new report.

“To guarantee the safe use of TKIs, ‘a drugs review for each patient is needed,’ write Frank G.A. Jansman, PharmD, PhD, from Deventer Hospital in the Netherlands, and colleagues in a review published in the July issue of the Lancet Oncology.

“The review provides a comprehensive overview of known and suspected interactions between TKIs and conventional prescribed drugs, over-the-counter drugs, and herbal medicines.

“All 15 TKIs approved to date by the US Food and Drug Administration or the European Medicines Agency are evaluated.

“They are axitinib (Inlyta, Pfizer), crizotinib (Xalkori, Pfizer), dasatinib (Sprycel, Bristol-Myers Squibb and Otsuka America), erlotinib (Tarceva, Osi Pharmaceuticals), gefitinib (Iressa, AstraZeneca), imatinib (Gleevec, Novartis), lapatinib (Tykerb, GlaxoSmithKline), nilotinib (Tasigna, Novartis), pazopanib (Votrient, GlaxoSmithKline), regorafenib (Stivarga, Bayer), ruxolitinib (Jakafi, Incyte), sorafenib (Nexavar, Bayer), sunitinib (Sutent, Pfizer), vandetanib (Caprelsa, AstraZeneca), and vemurafenib (Zelboraf, Roche).”


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.