Navigation Links
MGH-led studies shed new light on targeted lung cancer therapy
Date:6/1/2013

Research teams led by Massachusetts General Hospital (MGH) Cancer Center investigators are publishing two important studies regarding use of the targeted cancer drug crizotinib for treatment of advanced lung cancer driven by specific genetic mutations. The first reports the final results of a global, phase 3 trial showing that crizotinib is superior to standard chemotherapy for treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). The second paper describes the first report of resistance to crizotinib treatment in a patient with ROS1-positive NSCLC and reveals the mechanism underlying that resistance. Both papers are being published online in the New England Journal of Medicine to coincide with the American Society of Clinical Oncology annual meeting.

One of a group of drugs that directly targets genetic mutations spurring the uncontrolled growth of cancer, crizotinib has regulatory approval for the treatment of advanced NSCLC driven by rearrangements of the ALK gene and is being investigated for treatment of tumors driven by the MET and ROS1 genes. While previous studies showed that crizotinib was effective in treating ALK-positive lung cancer, the activity of standard chemotherapy against that type of tumor -- which had only recently been described -- was not known.

"This is the first randomized study to compare crizotinib with standard chemotherapy in advanced ALK-positive lung cancer," says Alice Shaw, MD, PhD, of the MGH Cancer Center, the first author and lead investigator for the study. "This study supports the full FDA approval of crizotinib in the U.S. and has also led to approval of crizotinib in many countries around the world." Preliminary results from this trial were first reported at the European Society for Medical Oncology meeting in September 2012.

The trial enrolled 347 patients with advanced ALK-positive NSCLC that had progressed after first-line treatment. Participants were randomly assigned to receive either oral crizotinib twice a day or standard chemotherapy with the intravenous drugs pemetrexed or docetaxel, given once every three weeks. Patients in the chemotherapy group whose tumors progressed were allowed to cross over to receive crizotinib.

Compared to chemotherapy, crizotinib more than doubled the average progression-free survival, from 3 months with chemotherapy to 7.7 months. The response rate with crizotinib was 65 percent, more than triple that of chemotherapy. Crizotinib more powerfully suppressed and prevented the recurrence of symptoms and resulted in significantly greater quality-of-life improvements. While overall survival rates for both groups were quite similar, more than 60 percent of those in the chemotherapy group eventually began receiving crizotinib which, the authors note, probably confounded the survival analysis.

"This study shows that patients with advanced ALK-positive lung cancer respond better to crizotinib and for longer periods of time," Shaw says. "Equally important, patients treated with crizotinib report better symptom control and quality of life than those treated with chemotherapy." Another ongoing phase 3 trial is comparing crizotinib to chemotherapy as first-line treatment for newly diagnosed patients.

The second paper describes an NSCLC patient who was treated with chemotherapy after initial genetic studies found none of the tumor-associated mutations known at the time. When her cancer continued to progress, additional molecular testing identified a rearrangement in ROS1 that Shaw and her colleagues had only recently described and shown could be treated with crizotinib. At first, the patient's tumor responded quickly, with symptomatic improvement after less than a week of crizotinib therapy. But after three months symptoms returned and her tumor resumed growing, eventually leading to the patient's death.

While the development of resistance to targeted cancer therapies is common, this is the first report of crizotinib resistance in ROS1-positive NSCLC. Detailed molecular analysis revealed a secondary mutation in the initial ROS1 rearrangement. The researchers then determined exactly how crizotinib binds to the ROS1 protein and showed that the new mutation, which is similar to one that confers resistance in ALK-positive tumors, interferes with binding and prevents the drug from inhibiting ROS1-driven tumor growth. Postmortem samples found this resistance mutation in every site to which the tumor had spread.

"Finding that mutation at all sites of disease suggests that it was an early and critical event in the development of resistance," says Jeffrey Engelman, MD, PhD, of the MGH Cancer Center, one of the senior authors of the study. "A similar and highly resistant mutation also occurs in ALK-positive tumors treated with crizotinib, so finding therapies that can overcome this particular type of mutation will be very important."


'/>"/>

Contact: Katie Marquedant
kmarquedant@partners.org
617-314-3986
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. Studies Shows “Fat Talkers” Are Less Liked by Peers
2. Zane Benefits Publishes New HRA Case Studies
3. Mayo Clinic: Scheduled imaging studies provide little help detecting relapse of aggressive lymphoma
4. Icahn School of Medicine at Mount Sinai and Bene Pharmachem Gmbh to Collaborate on Clinical Studies for Mucopolysaccaridoses
5. Salt Institute: IOM Admits Sodium Reduction May Cause Harm, More Studies Needed
6. Typical Restaurant Meal Loaded With Fats, Salt, Calories: Studies
7. New Studies Examining Positive Connections Between Diet Rich in Wild Blueberries and Better Brain Health
8. Case Studies, Best Practices of Companies Operating Private Exchanges to Be Reviewed in May 14 Webinar
9. Cancer studies often lack necessary rigor to answer key questions
10. International Narconon Directors Join Parents of Graduates to Celebrate Release of 40 Years of Positive Outcome Studies
11. Gene Studies Could Point to New Alzheimers Treatments
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/26/2016)... , ... May 26, 2016 , ... ... Degeneration” for the Foundation Fighting Blindness, Long Island Chapter on June 4, 2016, ... public. , Dr. Maisel, founder of Retina Group of New York , ...
(Date:5/26/2016)... (PRWEB) , ... May 26, 2016 , ... In an effort to provide hair restoration ... to both Snapchat users and those who do not use the app. Dr. Mohebi, the ... new page, Dr. Mohebi Live . , Dr. Mohebi says, “The positive response ...
(Date:5/26/2016)... ... May 26, 2016 , ... Leadership ... solutions, today announced the organization has earned its ISO 13485 certification, indicating the ... compliant with all rules and policies associated with ISO quality standard 13485. ...
(Date:5/26/2016)... ... ... The Lung Institute has partnered with the Gulfcoast North Area ... at their clinic in downtown Tampa. The class is complimentary for the public. Register ... a free downloadable 4 Week Smoking Cessation Guide for those who are ...
(Date:5/26/2016)... ... May 26, 2016 , ... Nike Yoga Camps ... from daily practices, arts & crafts, discussions, and games all geared towards enhancing ... Evans have combined backgrounds in kids’ yoga, collegiate sport yoga instruction, and global ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... 2016 As illustrated by the ... month, the numbers and momentum of cannabis in the ... the billions, more research and development push the sector ... of Legal Marijuana Markets Report  from from ArcView Market ... of the increase in sector is attributed to adult ...
(Date:5/25/2016)... MedDay, a biotechnology company focused on the treatment ... "High doses of biotin in progressive multiple sclerosis: extension phase ... Ayman Tourbah , Principal Investigator of the Phase 3 ... Neurology (EAN) in Copenhagen, Denmark . The ... on Sunday, 29 May 2016 from 14:45 to 16:15 CEST ...
(Date:5/24/2016)... AMSTERDAM , May 24, 2016 ... auf den Markt gebracht, die es Ärzten erlaubt, ... überall zu behandeln: MDLinking kombiniert Live Streaming mit ... sicheren Umfeld zu kommunizieren. Mediziner in Europa, Afrika, ... haben sich bereits für die Plattform registriert. ...
Breaking Medicine Technology: