Studies Reveal Potential New Targeted Therapies for Common, Hard-to-Treat Cancers

ASCO Annual Meeting Features Key Advances in Ovarian, Lung and Thyroid Cancers and Leukemia

May 31, 2014

Kelly Baldwin
(312) 949-3232 

CHICAGO – Positive results from four clinical trials of investigational targeted drugs for advanced ovarian, lung, and thyroid cancers, and chronic lymphocytic leukemia were highlighted today at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO). Findings from the mid- and late-stage trials suggest new ways to slow disease progression and improve survival for patients who experience relapses or resistance to available treatments.

"Cancer relapses and treatment resistance have always been among the most daunting challenges in cancer care," said press briefing moderator 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 research highlighted today 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."

Key studies include:

  • Second-line treatment with ramucirumab plus standard docetaxel extends survival for patients with advanced non-small cell lung cancer: This phase III clinical trial marks the first time in a decade that a survival benefit has been achieved in second-line therapy for patients with advanced non-small cell lung cancer – findings that could impact the care of 60,000 patients each year in the United States.
  • Ibrutinib is highly active, significantly delaying disease progression and extending survival for patients with resistant or relapsed chronic lymphocytic leukemia: Early results from the RESONATE study reveal the first oral agent to improve survival for resistant or relapsed CLL.  Treatment was well tolerated, affirming ibrutinib as an important new option for this common adult leukemia, especially for elderly patients who are often unable to tolerate traditional chemotherapy.
  • New targeted drug, lenvatinib, yields high response rates, delays progression in patients with radioiodine-resistant, advanced differentiated thyroid cancer: Nearly two-thirds of patients responded to lenvatinib treatment, which also delayed disease progression by 14.7 months over placebo.
  • A new targeted drug combination, cediranib plus olaparib, significantly increases progression-free survival in women with recurrent ovarian cancer: A combination of the PARP inhibitor olaparib and the anti-angiogenic drug cediranib delays recurrent ovarian cancer progression by more than eight months compared with olaparib alone. This marks the first time these two types of targeted drugs have ever been combined, and could fill an important gap in treatment of ovarian cancer.

Media Resources:

  • Online Annual Meeting Media Resource Center: Visit for press releases, press briefing recordings, the press briefing schedule at-a-glance, embargo policies, high-resolution photos, print-friendly downloads, and the Virtual Press Room, an online repository of corporate and institutional press releases from third-party organizations. 
  • CancerProgress.Net: The home of ASCO's 50th Anniversary and a timeline detailing the progress made against 18 of the most common cancers. 
  • Cancer.Net: ASCO's cancer information website, providing doctor-approved information on more than 120 cancer types.

The Annual Meeting Media Resource Center will be updated frequently leading up to and throughout the Annual Meeting.


Click here to view the disclosures for the 2014 ASCO Annual Meeting News Planning Team.

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About ASCO
Founded in 1964, the American Society of Clinical Oncology (ASCO) is the world’s leading professional organization representing physicians who care for people with cancer. With nearly 35,000 members, ASCO is committed to improving cancer care through scientific meetings, educational programs and peer-reviewed journals. ASCO is supported by its affiliate organization, the Conquer Cancer Foundation, which funds ground-breaking research and programs that make a tangible difference in the lives of people with cancer.  For ASCO information and resources, visit Patient-oriented cancer information is available at

Second-Line Treatment With Ramucirumab Plus Standard Docetaxel Extends Survival for Patients With Advanced Non-Small Cell Lung Cancer

Findings from the REVEL phase III study of patients with stage IV non-small cell lung cancer (NSCLC) indicate that a combination of a new anti-angiogenesis drug, ramucirumab, and standard docetaxel chemotherapy extends overall survival for patients who have a relapse after initial treatment compared to docetaxel plus placebo. The median overall survival was 10.5 months in the ramucirumab arm compared to 9.1 months in the placebo arm.

“This is the first treatment in approximately a decade to improve the outcome of patients in the second-line setting,” said lead study author Maurice Pérol, MD, Head of Thoracic Oncology at Cancer Research Center of Lyon in France. “The survival improvement is significant because patients with advanced NSCLC typically have a very short survival time following second-line therapy.”

Ramucirumab is a monoclonal antibody that specifically targets a protein called VEGF receptor 2, blocking growth of new blood vessels in the tumor (angiogenesis). No other approved anti-angiogenesis drugs are available in the second-line setting for advanced NSCLC, and currently ramucirumab is approved only for advanced gastric cancer treatment.

There is a large unmet medical need in the second-line treatment of advanced NSCLC, as all patients eventually experience a relapse following initial therapy. Approved second-line therapies for advanced NSCLC include docetaxel, erlotinib, and pemetrexed (for non-squamous NSCLC only), though clinical outcomes remain poor, with tumor shrinkage rates around 10 percent and median overall survival ranging between seven and nine months.

In the study, 1,253 patients with stage IV NSCLC (26 percent had the squamous subtype) that had progressed despite standard platinum-based therapy were randomly assigned to treatment with ramucirumab plus docetaxel or placebo plus docetaxel.

The addition of ramucirumab improved the efficacy of second-line docetaxel therapy – 22.9 percent of patients experienced tumor shrinkage in the ramucirumab arm compared to 13.6 percent in the placebo arm. The median overall and progression-free survival periods were 10.5 and 4.5 months in the ramucirumab plus docetaxel arm vs. 9.1 and 3 months in the placebo plus docetaxel arm, respectively. The survival benefits were consistent in the major subgroups of patients, including squamous and non-squamous subtypes, suggesting that this therapy could be suitable for all major subtypes of NSCLC. The safety profile was as expected for an anti-VEGFR agent in combination with docetaxel, with no increase in the rate of pulmonary hemorrhage (acute bleeding from the lung).

This research was supported by ImClone, a wholly owned subsidiary of Eli Lilly.


ASCO Perspective:
“This study expands the treatment options for patients with recurrent or refractory non-small cell lung cancer,” said Gregory A. Masters, MD, ASCO Expert. “Ramucirumab is an effective targeted agent when added to chemotherapy, with low toxicity. This will be a significant benefit to those patients whose cancer progresses following initial chemotherapy.”

Relevant links from Cancer.Net, the oncologist-approved cancer information website from the American Society of Clinical Oncology:


Relevant links from CancerProgress.Net, the home of ASCO's 50th Anniversary and progress made against 18 of the most common cancers:

To view the full abstract, click here.

Ibrutinib Is Highly Active, Significantly Delaying Disease Progression and Extending Survival for Patients With Resistant or Relapsed Chronic Lymphocytic Leukemia

Summary contains updated data not included in the abstract

Early findings from the phase III RESONATE study indicate that ibrutinib yields lasting tumor responses and marked improvement in survival over standard ofatumumab for patients with relapsed chronic lymphocytic leukemia (CLL). This is the first time an oral drug has demonstrated a survival improvement over standard therapy in relapsed CLL.  Just as important, the therapy was well tolerated by patients, causing few serious side effects.

CLL is the most common form of leukemia in adults. The standard treatment for CLL is chemo-immunotherapy, a combination of intensive chemotherapy and an antibody such as rituximab. However, elderly patients, who account for the majority of patients with CLL, often cannot tolerate intensive chemotherapy. Ofatumumab is an alternative option for such patients, but studies have shown it is much less effective than intensive chemotherapy. 

“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.” 

Ibrutinib was FDA approved for the treatment of CLL in February of this year, through the FDA’s accelerated review process, less than five years after entering phase I clinical trials.

In the study, 391 patients with relapsed or refractory CLL or small lymphocytic lymphoma (a subtype of CLL) that had progressed after two or more prior therapies were randomly assigned to treatment with ofatumumab or ibrutinib. The median patient age was 67 years, and 40 percent were older than 70 years.

At a median follow-up of 9.4 months, the response rates were dramatically higher in the ibrutinib arm compared to the ofatumumab arm (42 percent vs. 4 percent). An additional 20 percent of patients treated with ibrutinib had a partial response with persistent lymphocytosis (increase in white blood cells called lymphocytes). Ibrutinib was associated with an 80 percent lower risk of disease progression and a 57 percent lower risk of dying compared to ofatumumab; the median progression-free and overall survival have not been reached. Ibrutinib had similarly high activity in two very high-risk groups of patients (17p deletions and purine analog refractory).

Based on these striking early results, patients in the ofatumumab arm were offered the opportunity to cross over to the ibrutinib arm, and patient follow-up continues. According to the researchers, the median overall survival is expected to be in the range of several years.

Overall, both ibrutinib and ofatumumab were well tolerated. Diarrhea, minor bleeding, and atrial fibrillation were more common in the ibrutinib arm, whereas peripheral neuropathy was more common in the ofatumumab arm. This study alleviated concerns about kidney problems that were raised in the phase II ibrutinib study.

This research was supported by Pharmacyclics.

ASCO Perspective:
“This phase III study in relapsed refractory chronic lymphocytic leukemia confirms that ibrutinib, administered orally, has significant efficacy and is well-tolerated," said Olatoyosi Odenike, MD, ASCO Expert. "These results provide a compelling new treatment option for patients with chronic lymphocytic leukemia, including older adults with this disease, and will significantly change practice."

Relevant links from Cancer.Net, the oncologist-approved cancer information website from the American Society of Clinical Oncology:


Relevant links from CancerProgress.Net, the home of ASCO's 50th Anniversary and progress made against 18 of the most common cancers:

To view the full abstract, click here.

New Targeted Drug, Lenvatinib, Yields High Response Rates, Delays Progression in Patients With Radioiodine-Resistant, Advanced Differentiated Thyroid Cancer

Findings from the SELECT phase III study show that lenvatinib is highly effective against differentiated thyroid cancer that is resistant to standard radioiodine (RAI) therapy. The new oral targeted drug delayed disease progression by 14.7 months, and nearly two thirds of patients experienced tumor shrinkage. The median overall survival has not been reached.

“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.”

Differentiated thyroid cancer is the most common subtype of thyroid cancer, accounting for about 85 percent of the 60,000 thyroid cancer cases diagnosed each year in the United States. Although differentiated thyroid cancer is generally curable with standard treatment – surgery and RAI – roughly 5-15 percent of patients develop RAI resistance. Another targeted drug called sorafenib was approved by the FDA in November 2013 to treat this same population of patients.

Lenvatinib is an oral tyrosine kinase inhibitor that blocks several targets in a cancer cell, including VEGFR1-3, FGFR 1-4, PDGFR-β, KIT, and RET. It is being explored in phase II and phase III clinical trials as a potential treatment for liver, lung, and kidney cancers and other types of solid tumors.

In this study, 392 patients with advanced, RAI-resistant, differentiated thyroid cancer that had progressed within a year were randomly assigned to treatment with either lenvatinib or placebo. Patients on the placebo arm were allowed to cross over to the lenvatinib arm upon disease progression. 

Approximately 65 percent of patients experienced tumor shrinkage in the lenvatinib arm, compared to only 3 percent in the placebo arm. The majority of responses occurred within two months of starting treatment. The median progression-free survival was 18.3 months in the lenvatinib arm vs. 3.6 months in the placebo arm. The median overall survival has not been reached.

The five most common side effects of lenvatinib were high blood pressure, diarrhea, decreased appetite, decreased weight, and nausea. Although the side effects necessitated dose reductions in 78.5 percent of patients, the benefit of lenvatinib persisted with decreased dose, Dr. Schlumberger noted.

This research was supported by Eisai Inc.

ASCO Perspective:
“The progress we’re seeing with targeted agents for uncommon cancers is encouraging, said Gregory A. Masters, MD, ASCO Expert. “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.” 


Relevant links from Cancer.Net, the oncologist-approved cancer information website from the American Society of Clinical Oncology:


Relevant links from CancerProgress.Net, the home of ASCO's 50th Anniversary and progress made against 18 of the most common cancers:

To view the full abstract, click here.

A New Targeted Drug Combination, Cediranib Plus Olaparib, Significantly Increases Progression-Free Survival in Women With Recurrent Ovarian Cancer

Summary contains updated data not included in the abstract

Findings from a federally funded, NCI-sponsored phase II study suggest that the combination of two investigational oral drugs, the PARP inhibitor olaparib and the anti-angiogenesis drug cediranib, is significantly more active against recurrent, platinum chemotherapy-sensitive disease or ovarian cancer related to mutations in BRCA genes than olaparib alone. The progression-free survival was 17.7 months with the combination treatment vs. nine months with olaparib alone.

“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.”

This study is the first time a combination of a PARP inhibitor and an anti-angiogenic drug has ever been explored in a clinical trial for ovarian cancer. (PARP is an enzyme involved in many functions in a cell, including repair of DNA damage. Inhibition of PARP may cause cancer cells to die. Anti-angiogenic drugs block the growth of blood vessels in the tumor.)  It confirms preclinical research which suggested that olaparib and cediranib synergize, meaning they work together to make each other more active. Dr. Liu and her colleagues designed this trial to confirm, in a clinical setting, that the combination of these two drugs was more active than the single drug olaparib alone.

As many as 80 percent of women with high-grade serous ovarian cancer experience a relapse after initially responding to chemotherapy. When the cancer comes back, it is more difficult to treat, because it will have spread to the pelvis and abdomen, or even the lungs. The current standard treatment for recurrent ovarian cancer is chemotherapy, which often causes significant side effects.  Even in the setting of initial response, resistance to chemotherapy eventually develops. Therefore, researchers have been exploring alternate regimens using targeted drugs, with the goal of overcoming such treatment resistance.

Ninety women with recurrent, platinum-sensitive (disease that responds to treatment with platinum-based chemotherapy), high-grade serous or BRCA mutation-related ovarian cancer, were randomly assigned to treatment with olaparib alone or olaparib plus cediranib. The women had no prior treatment with anti-angiogenic drugs in the setting of recurrent ovarian cancer or PARP inhibitors.

Tumor shrinkage rates were markedly higher in the combination arm than in the olaparib arm (80 vs. 48 percent). Five patients in the combination arm and two patients in the olaparib alone arm had a complete remission. The combination treatment substantially delayed disease progression, with a progression-free survival of 17.7 months compared to nine months for olaparib alone. Past trials of standard chemotherapy in the platinum-sensitive setting have demonstrated progression-free survival times between eight and 13 months.

Although certain side effects ─ high blood pressure, fatigue, and diarrhea ─ occurred more frequently in the combination arm, they were usually controllable by symptom management and dose reductions as needed.

Prior trials have suggested that PARP inhibitors tend to have the most activity in women who have either platinum-sensitive ovarian cancer or BRCA mutations in their tumors. An exploratory analysis from this study suggests that the combination treatment appears to also be active in patients without a known BRCA-mutation. Dr. Liu remarked that it is reasonable to explore whether the combination treatment would be effective in women with platinum-resistant disease as well.

This study was supported by the National Cancer Institute, National Institutes of Health.

*Dr. Liu is the recipient of a 2008 Conquer Cancer Foundation of ASCO Young Investigator Award.

ASCO Perspective:
“The combination of cediranib plus olaparib resulted in a significantly higher response rate, though at the expense of higher toxicity. Whether this response translates into gains in survival needs further follow-up,” said Don S. Dizon MD, FACP, ASCO Expert. “However, this combination represents an oral, non-chemotherapy-based combination treatment option for women with high-grade serous or BRCA-mutation related ovarian cancers and definitely warrants further study.”

Relevant links from Cancer.Net, the oncologist-approved cancer information website from the American Society of Clinical Oncology:


Relevant links from CancerProgress.Net, the home of ASCO's 50th Anniversary and progress made against 18 of the most common cancers:

To view the full abstract, click here.