Four clinical trials for investigational cancer therapies have shown positive results in combating advanced ovarian, lung, and thyroid cancers, as well as chronic lymphocytic leukemia. The results, which were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), have increased researchers’ hope for finding ways to slow down disease progression and improve survival rates.
“Cancer relapses and treatment resistance have always been among the most daunting challenges in cancer care,” said Gregory Masters, MD, FACP, ASCO Expert, and a medical oncologist at the Helen F. Graham Cancer Center in Newark, Delaware. “The good news is that genomic medicine is helping to overcome these challenges by revealing new ways to target a cancer cell’s inner workings. The highlighted research could lead to new treatment options for patients who, until now, have had none, or for whom the side effects of current drugs outweigh their limited benefits, as we often see with our older patients with leukemia.”
One of the new drugs, developed by Eli Lilly Company, is ramucirumab, which, combined with the traditional docetaxel chemotherapy, was able to prolong the lives of advanced non-small cell lung cancer patients six weeks longer compared to ones who only took chemotherapy. The phase III clinical trial for ramucirumab marks the first time in a decade that an experimental therapy has shown a survival benefit in second-line treatment for non-small cell lung cancer.
The drug developed by Lilly’s ImClone unit is a monoclonal antibody that targets a protein called VEGF receptor 2, and blocks the formation of the blood vessels that nourish tumor growth. Despite the seemingly negligible difference in prolonging the life of patients, researchers believe the results are statistically significant and clinically meaningful, since advanced lung cancer typically leads to extremely poor survival projections, after initial treatment. The findings could impact care of 60,000 patients each year in the country.
The clinical trial included 1,253 patients, with stage IV NSCLC (26 percent had the squamous subtype), who received either ramucirumab with the common chemotherapy drug docetaxel or just the chemotherapy. The first group lived on average 10.5 months, compared to the second group, which lived 9.1 months. Researchers verified the benefits of the drug were consistent with the presence of squamous or non-squamous forms of the disease, which proposes ramucirumab may be suitable for the major subtypes of non small cell lung cancer.
The second new study, RESONATE, which involved researchers from The University of Texas MD Anderson Cancer Center in Houston, revealed a new course of treatment for patients with resistant or relapsed chronic lymphocytic leukemia. The oral agent Ibrutinib is a highly active therapy that has proven to delay disease progression and extend survival. This is the first time an oral drug was demonstrated to provide survival improvements over standard therapy.
“With ibrutinib, about 80 percent of patients were still in remission at one year, twice as many as we would expect with standard therapy,” said lead study author John Byrd, MD, a professor of medicine at The Ohio State University Comprehensive Cancer Center in Columbus, Ohio. “Although the follow-up was short in this study, the data definitely support the use of ibrutinib before anything else in this setting.”
The standard treatment for patients who suffer from the most common form of leukemia in adults is chemo-immunotherapy. However, a large number of patients don’t tolerate the intensive treatment and take the alternative Ofatumumab, but studies reveal it is much less effective. Researchers believe Ibutrinib may be a new option for the common adult disease, especially among older people who are most likely to not tolerate traditional chemotherapy.
The study included 391 patients with relapsed or refractory CLL or small lymphocytic lymphoma, and the results showed they progressed after two or more prior therapies. The patients, which had a median age of 67, were randomly administered either atumumab or ibutrinib.
In a third clinical trial, Nearly two-thirds of the patients responded positively to Ienvatinib, which delayed thyroid cancer progression by 14.7 months over placebo. Findings from the SELECT phase III study reveal that the new drug is highly effective in patients with radioiodine-resistant (RAI) and advanced differentiated tumors (the most common subtype of thyroid cancer and commonly treated with surgery and radiotherapy). Tumor shrinkage was observed as well among 65% of the 392 patients analyzed.
“We are confident that, based on our findings, lenvatinib will eventually become a standard treatment for radioiodine-resistant thyroid cancer,” said lead study author Martin Schlumberger, MD, a professor of oncology at the University Paris Sud in Paris, France. “As little as a year ago, this group of patients had no effective treatment options. It’s remarkable that we now have two active drugs in this setting, both of them tyrosine kinase inhibitors.”
Considering that between 5 and 15% of patients develop RAI resistance, the oral tyrosine kinase inhibitor may be an alternative option. The drugs works by blocking several targets in a cancer cell, and it may be used as a potential treatment for liver, lung, and kidney cancers as well. “The progress we’re seeing with targeted agents for uncommon cancers is encouraging,” said Gregory A. Masters adding that “patients with differentiated thyroid cancer have historically had limited options when the disease progresses despite radioactive iodine therapy. Now this new drug, lenvatinib, offers an effective option with reasonable side effects and can help patients live longer before the disease worsens.”
In the fourth clinical trial presented at ASCO, a new targeted combination of two investigational oral drugs has been proved more active to combat recurrent, platinum chemotherapy-sensitive disease or ovarian cancer related to mutations in BRCA genes. The drugs are the PARP inhibitor olaparib and the anti-angiogenesis drug cediranib, which increased the progression-free survival from nine (on patients treated only with olaparib) to 17.7 months. This is the first time these two drugs were combined and could mean an important development in treating ovarian cancer.
“The significant activity that we saw with the combination suggests that this could potentially be an effective alternative to standard chemotherapy,” said lead study author Joyce Liu, MD, MPH, an instructor in medical oncology at Dana-Farber Cancer Institute in Boston, MA. “At the same time, this approach is not yet ready for clinical practice as neither of these drugs is currently FDA approved for ovarian or any other cancer. We also need additional clinical trials to confirm the findings of this study to see how this combination compares to standard treatment.”
Both drugs activated each other’s effects and were able to minimize tumors in 80% of the patients. A large number of women with high-grade serious ovarian cancer suffer a relapse after initial chemotherapy, which is more difficult to treat because by then the disease will have spread to the pelvis and abdomen. Eventually they can develop chemotherapy-resistance.
This year’s ASCO has produced a wealth of new cancer treatment possibilities that could very well pave the way toward a next generation of therapies that do not necessarily involve radiation, chemotherapies, and other current therapeutic options. For researchers, the new data gives them jumping-off points for new research projects. For cancer patents, the positive results are a welcome sign that doctors are getting closer to controlling and even curing cancer at its root.