Targeted Therapies Beneficial in KRAS-Mutated NSCLC

Excerpt:

“Targeted therapies that do not contain erlotinib can be beneficial for patients with KRAS-mutated (KRAS mut+) advanced non-small-cell lung cancer (NSCLC), according to a study published online Aug. 1 in the Journal of Clinical Oncology.

“Vassiliki Papadimitrakopoulou, M.D., from the University of Texas MD Anderson Cancer Center in Houston, and colleagues examined the effects of targeted therapies in NSCLC. Patients were randomized to four arms: erlotinib (22 patients), erlotinib plus MK-2206 (42 patients), MK-2206 plus AZD6244 (75 patients), or sorafenib (61 patients).

“The researchers found that the primary end point of an eight-week disease control rate (DCR) was 48 percent in all 186 evaluable patients (32, 50, 53, and 46 percent, respectively, for the four treatment arms). For the 27 percent of patients who were KRAS mut+, DCR was 20, 25, 62, and 44 percent, respectively, compared with 36, 57, 49, and 47 percent, respectively, for KRAS wild-type patients. Median progression-free survival was 2.0 months: 1.8 and 2.5 months for arms 1/2 and 3/4, respectively, in KRAS mut+ patients (P = 0.04). In KRAS wild-type patients, median overall survival was 6.5 months: 9.0 and 5.1 months in arms 1/2 and 3/4, respectively (P = 0.03).”

Go to full article.

Do you have questions about this story? Let us know in a comment below. If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our Ask Cancer Commons service.


Drugs That Work in Melanomas with BRAF Mutation Also Work in Lung Cancers with Same Mutation

“A subset of lung cancer patients can derive important clinical benefits from drugs that are more commonly used to treat melanoma, the authors of a new academic clinical trial in Europe have reported at the European Lung Cancer Conference (ELCC) in Geneva, Switzerland.

“Dr. Oliver Gautschi, a medical oncologist from Lucern Cantonal Hospital in Switzerland, presented the results of the retrospective EURAF cohort study, which included lung cancer patients whose tumours carried specific mutations in the BRAF gene. The study was conducted by a network of European oncologists, without company involvement.

“BRAF mutations are commonly seen in melanoma patients, and are found in about 2% of lung adenocarcinomas, Gautschi explains. Several inhibitors of the B-Raf protein, including vemurafenib and dabrafenib, have been developed for use in melanoma patients, however there is currently no approved drug for BRAF-mutant lung cancer.

“As a result, experience with B-Raf inhibitors in lung cancer remains limited. ‘In the current study, we wanted to find out how many patients in Europe received B-Raf inhibitors outside of a clinical trial, and what their outcomes were,’ Gautschi says.

“The EURAF study gathered information on 35 lung cancer patients who had been identified as carrying BRAF mutations, who were treated with B-Raf inhibitors between 2012 and 2014.”


Phase II Trial Shows Overall Survival Benefit With VT-122 Plus Sorafenib in Advanced Hepatocellular Carcinoma

The gist: People with advanced hepatocellular carcinoma may benefit from treatment with a combination of the drugs VT-122 and sorafenib (Nexavar). That was the conclusion of a recent clinical trial—a research study with volunteer patients. The goal of the trial was to test the combination treatment. In the trial, people who took the combination had an 11-month increase in overall survival compared to people who took only sorafenib.

“The investigational agent VT-122 appeared to benefit survival when combined with sorafenib (Nexavar) in patients with advanced hepatocellular carcinoma, according to data presented at the 8th Annual International Liver Cancer Association Conference in Kyoto, Japan. Researchers reported an 11-month increase in median overall survival in patients treated with VT-122 plus sorafenib, compared to those receiving sorafenib alone.

“VT-122 is a novel, oral, chronodosed combination of the nonsteroidal anti-inflammatory drug (NSAID) etodolac and the beta-blocker propranolol. The investigational compound inhibits prostaglandin and beta-adrenergic signaling to reduce tumor-promoting inflammation and restore a tumor-suppressing immune state…

“In this phase II randomized, open-label, controlled clinical trial, 24 patients with advanced hepatocellular carcinoma were randomly assigned to receive VT-122 plus sorafenib or sorafenib alone.”


Trial Shows Improved Overall Survival for Patients with Liver Cancer not Amenable to Surgery

The gist: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test a new treatment for people with inoperable advanced hepatocellular carcinoma (HCC). The new treatment combines two existing treatments: a chemotherapy drug called sorafenib and Selective Internal Radiation Therapy (SIRT). The results of the trial showed improved survival for the patients who participated. The new treatment will continue to be tested in the hopes that it may prove good enough to be widely used to treat advanced HCC.

“The mature results from a trial conducted by the Asia-Pacific Hepatocellular Carcinoma Trials Group led by the National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH) have shown that patients who suffer from inoperable advanced hepatocellular carcinoma (HCC) may have a chance to live significantly longer by using a combined therapy.

“The multi-centre phase II clinical trial was conducted at four Asia Pacific tertiary medical centres to evaluate the efficacy of combining two existing treatment modalities, Sorafenib and Selective Internal Radiation Therapy (SIRT). The combination therapy involves starting patients on SIRT using SIR-Spheres microspheres, a medical device that contains radioactive microspheres labeled with yttrium-90 for short range high energy radiation therapy, followed by systemic therapy with an oral chemotherapy drug, Sorafenib, 14 days later.

“The mature results of the trial published recently in a peer-reviewed journal, PLOS ONE, show that median overall survival was 20.3 months for patients with intermediate stage HCC and 8.6 months for patients with advanced liver cancer. These final results were better than the preliminary data released in 2010.”


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).”


Drug Everolimus Does Not Improve Overall Survival in Patients with Advanced Liver Cancer

“Despite strong preclinical data, the drug everolimus failed to improve overall survival in patients with advanced liver cancer, compared to placebo, according to a study in the July 2 issue of JAMA.

“Patients with advanced hepatocellular carcinoma (HCC; a type of liver cancer) have a median overall survival of less than l year, largely because of the absence of effective therapies. The drug sorafenib is the only systemic therapy shown to significantly improve overall survival in advanced HCC; however its benefits are mostly transient and modest, and disease eventually progresses. In preclinical models, everolimus prevented tumor progression and improved survival, according to background information in the article.

“Andrew X. Zhu, M.D., Ph.D., of the Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, and colleagues randomly assigned 546 adults with advanced HCC whose disease progressed during or after sorafenib or who were intolerant of sorafenib to receive everolimus (n = 362) or placebo (n = 184), both given in combination with best supportive care and continued until disease progression or intolerable toxicity. In this phase 3 study, patients were enrolled from 17 countries between May 2010 and March 2012.

“The researchers found no significant difference in overall survival between the two groups…”

Editor’s note: This article describes a clinical trial with volunteer patients to test a potential new liver cancer drug called everolimus. Patients in the trial all had advanced hepatocellular carcinoma (HCC) and had been unsuccessfully treated with sorafenib. Half were given everolimus, and for comparison, half were given a “fake” placebo drug. Unfortunately, there was no significant difference in survival between the two groups.


18F-FGD-PET Measures Predict mRCC TKI Response

“Positron emission tomography (PET) could be used to predict the response of metastatic renal cell carcinoma (mRCC) to tyrosine kinase inhibitor (TKI) therapy within a couple of weeks of a patient beginning treatment, research suggests.

“Changes in volume-based metabolic parameters of 18F-fluorodeoxyglucose (FDG) before and after 14 days of treatment with sunitinib, sorafenib or pazopanib significantly correlated with progression-free and overall survival, say Jacob Farnebo (Karokinska University Hospital, Stockholm, Sweden) and co-authors.”

Editor’s note: Doctors and patients can make more informed treatment decisions if they can more closely monitor how well a treatment is working and predict how well it is likely to work in the long run. This story discusses how monitoring with positron emission tomography (PET) within the first couple of weeks of treatment might help predict how well certain drugs will work. PET scanning produces 3-D images of the inside of the body. Scientists conducted a study in which they gave PET scans to volunteer patients who were being treated with the drugs sunitinib, sorafenib, or pazopanib for metastatic renal cell carcinoma (mRCC). They found that, within two weeks of the patients starting treatment, they could use information from the PET scans to determine the effectiveness of the treatment. They were able to link these PET scan results to how long the patients lived and how much time passed before patients’ disease worsened.


Study of 'Super Responder' Reveals New Oncogene for Lung Cancer

“Researchers have taken the next step in confirming the identity of previously unknown gene mutation that drives lung cancer development. Scientists at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) originally identified the mutation in one patient out of nine with advanced lung cancer who responded well to the drug sorafenib. The clinical trial involved 306 participants total.

“Within two months of beginning treatment, the patient had demonstrated a near complete response, and she remained progression-free and asymptomatic for five years while continuing to take sorafenib by mouth.”

Editor’s note: Different patients’ tumors have different genetic mutations. More and more, doctors are using patients’ tumor genetics to match patients with treatments that are most likely to work for them. Now, researchers have discovered a mutation called S214C, which may help doctors predict some lung cancer patients’ responses to treatment. The mutation was found in a patient in a clinical trial who responded particularly well to a drug called sorafenib.


Study of ‘Super Responder’ Reveals Possible New Gene Target for Lung Cancer

“A potential new gene mutation that might drive lung cancer development and growth has been identified by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James).

“A multi-institutional team led by OSUCCC-James researchers reports the findings in the Journal of Clinical Investigation. The study describes a patient with advanced lung cancer who was treated with the targeted drug sorafenib while on a clinical trial. Within two months, she demonstrated a near complete response, and she remained progression-free and asymptomic for five years while continuing to take sorafenib by mouth.”