When combined with standard chemotherapy, an international Phase III trial has shown that the oral targeted therapy vandetanib improves progression-free survival for patients with advanced non-small cell lung cancer, according to research from The University of Texas M. D. Anderson Cancer Center.
The findings, presented today at the American Society of Clinical Oncology's annual meeting, mark the first clinical benefit of a small molecule targeted agent and standard chemotherapy in combination for lung cancer. Roy Herbst, M.D., Ph.D., professor and chief of the section of M. D. Anderson's Department of Thoracic/Head and Neck Medical Oncology, presented the findings on ASCO's press program.
"This study shows that an oral tyrosine kinase inhibitor can be combined with chemotherapy safely and effectively to provide systematic benefit to patients with this life-threatening disease," said Herbst. "This study will have immediate clinical implications. Still, we need to build on this research and turn our focus toward better identifying molecular markers involved, with the ultimate goal of personalizing our patient's care."
The therapy is unique in that it's a dual inhibitor and targets the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR). It is the first single agent in lung cancer to target both receptors, said Herbst, the study's international principal investigator.
"Both receptors are active in lung cancer. EGFR targets the tumor cell and VEGF targets the blood vessels, so, with vandetanib, we're really targeting the entire tumor environment at the same time," explained Herbst. "As a dual inhibitor, it also may provide cost-savings to patients in that they can now potentially take one therapy instead of two."
According to the American Cancer Society, lung cancer accounts for the most cancer-related deaths. In 2009, 219,440 are expected to be diagnosed and 159,390 will likely die from the disease.
The ZODIAC, (Zactima in cOmbination with Docetaxel In non-smAll cell lung Cancer) study enrolled 1,391 patients with non-small cell lung cancer from 198 centers between May 2006 and April 2008; all had received chemotherapy previously. Participants were randomized to receive either docetaxel and placebo, or docetaxel and vandetanib. The median follow-up was 12.8 months and the study's primary endpoint was progression-free survival.
Patients in the combination arm had a 21 percent reduction in disease progression, compared to those who received docetaxel alone (hazard ratio, .79), and their median progression-free survival was 17.3 weeks. In contrast, the median progression-free survival in the control arm was 14 weeks. While it trended positive, however, there was no statistical difference in overall survival in the two groups. There was a statistically significant improvement in the time to worsening of symptoms (hazard ratio, .77).
"Obviously, our ultimate goal is to always improve survival for our patients, however the improved time to progression with less of a number of significant effects is important," said Herbst. "This is certainly a drug, where, if we could identify molecular parameters that predict response, we could some day take a group that's receiving docetaxel and vandetanib and see them do even better. We're not there yet, but hopefully this study will serve as the foundation for the merger of personalization and discovery with the now-proven safety and efficacy."
In terms of side effects, patients who received vandetanib experienced more diarrhea, rash and neutropenia. However, they experienced less of the significant side effects - nausea, vomiting, and anemia - than those who received docetaxel alone. The lack of significant side effects is quite striking, said Herbst, because other agents that target VEGF are associated with increased toxicity, including pulmonary bleeding.
As follow up, Herbst plans to update the survival data later this year. Other studies with vandetanib in lung cancer as a single agent, as well as in thyroid cancer, are currently ongoing.
In addition to Herbst, other authors on the study include: Yan Sun, Cancer Hospital, Bejing, China; Sönke Korfee, West German Tumor Center, University Duisburg-Essen; Paul Germonpré, Antwerp University Hospital, Belgium; Nagahio Saijo, National Cancer Center Hospital East, Chiba, Japan; Caichun Zhou, Tongji University, Shanghai, China; Jie Wang, Beijing Institute for Cancer Research, Beijing, China; Bruce Johnson, Dana-Farber Cancer Institute; and Peter Langmuir, Hiroomi Tada, Sarah Kennedy, all with AstraZeneca.
Herbst has been a consultant for and has received research support from AstraZeneca.
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For four of the past six years, including 2008, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.
Laura Sussman | EurekAlert!
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences