Combined MEK, BRAF Inhibitors Promising in Melanoma

The gist: Researchers have conducted a clinical trial with volunteer patients to test a new melanoma treatment that combines the drugs cobimetinib and vemurafenib. The participants all had melanoma tumors with BRAFV600 mutations. People with BRAFV600 mutations often become resistant to treatment if they take a “BRAF inhibitor” like vemurafenib. The hope is that drugs like cobimetinib can be given alongside vemurafenib to circumvent resistance. The researchers found that the combination treatment was safe for these patients, and there was some promising evidence that the treatment was effective, but more follow-up will be needed.

“Combined treatment of BRAFV600-mutated melanoma with the MEK inhibitor cobimetinib and the BRAF inhibitor vemurafenib was safe and tolerable, according to the results of a phase Ib study.

“Based on the promising antitumor activity seen with the combination, researchers led by Antoni Ribas, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, and colleagues recommended further clinical development and testing of this combination.

“According to background information published with the study in Lancet Oncology, patients with BRAFV600-mutated metastatic melanoma often develop resistance to treatment with a BRAF inhibitor, ‘which frequently reactivates the MAPK pathway through MEK.’ Prior research has shown that sequential treatment with a MEK inhibitor after this progression does not result in meaningful antitumor activity.”


Disturbing Discovery: New Generation of Targeted Cancer Drugs Cause Tumors To Become Drug Resistant and More Aggressive

Breast-cancer-cell

“In a modest-sized lab at the Moores Cancer Center at the University of California, San Diego, scientists investigating how cancer cells develop resistance to drug treatments recently discovered something that surprised even the most seasoned members of the research team: A new generation of drugs that are currently among the most popular treatments for lung, breast and pancreatic cancers actually induce drug resistance and spur tumor growth.

“These popular cancer drugs, known as receptor tyrosine kinase inhibitors (RTKs), are actually making cancers stronger. That’s the bad news. The good news is that researchers believe they have found a way to eliminate that threat.

“Researchers found that two of the drugs — Erlotinib for lung cancer and Lapatinib for breast cancer — are effective for a while, but eventually stop killing cancer cells and begin prompting them to resist the drug and become more aggressive.

“ ‘We knew that cancer typically builds up a resistance to these and other drugs. But we did not know that these drugs actually induce tumor progression,’ said David Cheresh, Moores’ vice chair of pathology and the lead researcher on this study.”

Image: A breast cancer cell. London Research Institute EM Unit/Cancer Research UK


ASCO 2014: Highlights for People Dealing with Melanoma


Every year, new cancer treatment insights are shared at the American Society of Clinical Oncology (ASCO) Annual Meeting. Here are some of the most notable recent developments in melanoma treatment, gleaned from researchers’ presentations at ASCO last month: Continue reading…


Blinatumomab Receives Breakthrough Therapy Designation for ALL

“The FDA has granted a breakthrough therapy designation to blinatumomab for the treatment of adult patients with Philadelphia-negative relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), according to Amgen, the company developing the drug.

“The breakthrough therapy designation was based on results from a phase II trial of 189 patients. As of January 2014, 43% (n = 82) of patients achieved a complete remission (CR) or CR with partial hematological recovery (CRh). These results were presented at the 2014 ASCO Annual Meeting and at the 19th Congress of the European Hematology Association.

” ‘There is a high unmet need for new medicines to treat relapsed and refractory ALL patients, who have very few treatment options,’ Sean E. Harper, MD, executive vice president, Research and Development, Amgen, said in a statement. ‘The results from the phase II trial evaluating blinatumomab in adult patients with relapsed or refractory ALL are encouraging and provide a strong basis for a regulatory filing later this year and potential approval in this serious disease.’ ”

Editor’s note: Blinatumomab is a new drug that is being tested as a potential treatment for people with acute lymphoblastic leukemia (ALL) that is resistant to treatment (refractory) or that has returned after treatment (relapsed). Based on promising research results, blinatumomab has received a Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA), specifically for adults with relapsed or refractory B-precursor ALL that is Philadelphia-negative. This means that the FDA finds the drug to be very promising compared to currently available treatments, and will accelerate the approval process that would ultimately permit U.S. oncologists to prescribe the drug outside of a clinical trial.


Phase III Trial Shows Improved Survival with TAS-102 in Metastatic Colorectal Cancer Refractory to Standard Therapies

“The new combination agent TAS-102 is able to improve overall survival compared to placebo in patients whose metastatic colorectal cancer is refractory to standard therapies, researchers said.

” ‘Around 50% of patients with colorectal cancer develop metastases but eventually many of them do not respond to standard therapies,’ said Takayuki Yoshino of the National Cancer Centre Hospital East in Chiba, Japan, lead author of the phase III RECOURSE trial. ‘The RECOURSE study shows that TAS-102 improves overall survival in these patients compared to placebo. I believe that this agent will become one of the standards of care in the refractory setting of metastatic colorectal cancer in Japan and worldwide.’

“TAS-102 is a novel nucleoside anti-tumour agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). FTD is the active component of TAS-102 and is directly incorporated into cancer DNA, leading to DNA dysfunction. However, when FTD is taken orally it is largely degraded to an inactive form. TPI prevents the degradation of FTD. This mechanism of action is different to that of fluoropyrimidine, oxaliplatin and irinotecan…

“Douillard concluded: ‘In RECOURSE, TAS-102 was tested in patients who had received all types of chemotherapy available for colorectal cancer. I would probably move this drug into an earlier line of treatment and I would also combine it with either irinotecan or oxaliplatin.’ ”

Editor’s note: This story discusses the results of a clinical trial that tested a new treatment for colorectal cancer in volunteer patients. The trial tested whether the treatment—called TAS-102—benefits people with metastatic cancer that has not responded to standard treatment. Some patients in the trial were treated with TAS-102, and for comparison, some were given a “fake” placebo treatment. The results showed that patients treated with TAS-102 survived longer than patients who took the placebo.


Clovis Launches TIGER2 Trial for CO-1686 in Previously Treated T790M-Positive NSCLC Patients

“Clovis Oncology has launched the TIGER2 study for its non-small cell lung cancer drug CO-1686, an agent the company is studying as a treatment for advanced patients with tumors characterized by EGFR mutations and the T790M resistance mutation.

“CO-1686 is an irreversible EGFR inhibitor. Clovis this week said it has dosed the first patient in the TIGER2 Phase I/II trial, which is focused on gauging the efficacy of CO-1686 in NSCLC patients who have progressed on their first and only anti-EGFR treatment.”

Editor’s note: Some people with advanced non-small cell lung cancer (NSCLC) have tumor cells with mutations in the EGFR gene (oncologists often use a tumor biopsy to check for this mutation in a patient). These patients can be treated with targeted drugs known as EGFR inhibitors. EGFR inhibitors can shrink tumors at first, but over time, tumors may become resistant to the drugs and start growing again. Often, this is because of a new, additional mutation that occurs in the EGFR gene called T790M. A new clinical trial is enrolling volunteer patients with the T790M mutation to test a new drug meant to overcome EGFR inhibitor resistance. The drug is called CO1-686.


ASCO 2014 — Takeaways for Prostate Cancer Patients


Every year, thousands of people gather for the American Society of Clinical Oncology (ASCO) Annual Meeting. This year’s meeting took place in Chicago, Illinois. Here are some of the most notable new developments in prostate cancer treatment presented at ASCO 2014: Continue reading…


At ASCO, Next-Gen EGFR Inhibitors Show Early Promise in Lung Cancer Patients with T790M Mutations

“Next-generation EGFR inhibitors for treating metastatic non-small cell lung cancer patients who have acquired resistance to first-generation drugs in this class accurately hit mutant EGFR tumor cells and caused fewer serious side effects, early data presented at a major cancer conference showed.

“Researchers at the American Society of Clinical Oncology’s annual meeting here this week, presented preliminary data from human studies on three next-generation EGFR inhibitors: AstraZeneca’s AZD9291, Clovis Oncology’s CO-1686, and Hanmi Pharmaceutical’s HM61713. All three agents showed promising activity against patients who had EGFR mutations, had received prior treatment with a first-generation tyrosine kinase inhibitor – such as Roche’s Tarceva (erlotinib) and AstraZeneca’s Iressa (gefinitib) – and had T790M mutations.”

Editor’s note: For a more reader-friendly explanation of these new drugs, check out the “Drug resistance” section of our Chief Scientist’s latest blog post.


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…