Updates from the annual meeting of the American Society of Clinical Oncology.
The American Society of Clinical Oncology (ASCO) hosted its annual meeting in Chicago from May 31 to June 4, attracting more than 32,000 cancer researchers, physicians, industry professionals, advocates and survivors to report on advances in cancer care, screening, treatment and prevention. For more coverage of the conference, visit curetoday.com/asco_2013.
The promise of training the body to recognize and kill cancer cells—without the side effects of traditional cancer therapies—has intrigued researchers for years. While a handful of immunotherapies are approved, a new class of drugs zero in on a protein called PD-1. This protein is present on the surface of activated T cells, immune cells that would ideally attack cancer cells. However, some cancer cells express PD-ligand 1 (PD-L1), which binds to PD-1, switching off the T cell and rendering cancer cells invisible to the immune system.
Several early-stage studies have given researchers confidence to move forward on certain PD-1 inhibitors, calling the drug class a "game changer" in melanoma. In a phase 1 study, participants who had been treated for advanced disease received the PD-1 inhibitor nivolumab with Yervoy (ipilimumab). While phase 1 studies look for safety issues and optimal dosing, this study found almost a third of patients had an 80 percent or greater reduction in tumor size. A phase 3 study in advanced melanoma is scheduled to begin this summer and might be the basis for approval.
A second PD-1 inhibitor, lambrolizumab, also showed impressive results with a 52 percent overall response rate in one cohort of patients. Another drug, MPDL3280A, binds to the cancer cells’ PD-L1, which prevents it from attaching to the T cell. More than a third of patients with incurable cancers, including melanoma, that expressed PD-L1 had a response to the drug as opposed to 13 percent of PD-L1-negative tumors. Further studies are planned to verify results.
"This work is going to change the state of the care of our patients with melanoma," said Walter J. Urba, director of cancer research at the Robert W. Franz Cancer Research Center in Portland, Ore., noting that treatment for melanoma has had many recent advances.
Because these drugs affect the immune system, researchers are concerned with inflammation-related or autoimmune side effects. However, they are excited about the efficacy and low toxicity of these drugs, which will need to be confirmed in larger trials. —Elizabeth Whittington
With the oral drug Votrient (pazopanib), women with advanced ovarian cancer may have a treatment that significantly extends time without disease progression thanks to positive results from a phase 3 study of patients with advanced epithelial ovarian, fallopian tube and primary peritoneal cancers.
In the study, 940 women were randomized to receive Votrient or a placebo daily for 24 months. All participants had stable disease after surgery and had been previously treated with at least five rounds of chemotherapy. The median time to disease progression was 17.9 months versus 12.3, with a gain of 5.6 months for those on Votrient. It is too soon to analyze survival benefits. More occurrences of hypertension were reported in the Votrient group.
Advanced ovarian cancer patients experience a cure rate of 20 to 25 percent with 70 percent relapsing, many in the first year. Currently, there are no maintenance therapies available for ovarian cancer in the U.S. Votrient, which works by affecting the growth of the tumor and its surrounding blood vessels, is already approved for advanced kidney cancer and advanced soft tissue sarcoma. —Kathy LaTour
Patients with multiple myeloma whose disease no longer responds to Velcade (bortezomib) or Revlimid (lenalidomide) or with relapsed disease may have another option with the recently approved immunomodulating agent Pomalyst (pomalidomide), a drug that works by inducing the immune system to attack and destroy myeloma cells.
The results of a phase 3 study involving 455 participants showed a significant survival benefit when adding Pomalyst to low-dose dexamethasone (a steroid) compared with high-dose dexamethasone alone. For participants taking Pomalyst plus low-dose dexamethasone, the time until their disease progressed was more than double that of participants in the high-dose group (a median of 4 months versus 1.9). Moreover, the combination was generally well-tolerated, with participants experiencing neutropenia (48 percent), anemia (33 percent) and infections (30 percent).
Because impaired kidney function is a common complication in patients with multiple myeloma, a second group of researchers analyzed the study data to determine the effectiveness of low-dose dexamethasone and Pomalyst in patients with or without kidney problems. The study concluded that response rates and survival outcomes were similar in patients, regardless of kidney function. —Jon Garinn
Researchers announced mixed results in a study of Erbitux (cetuximab) versus Avastin (bevacizumab) as a first-line treatment in patients with metastatic colorectal cancer without KRAS gene mutations. In the phase 3 German study, Erbitux came out ahead in overall survival when compared with Avastin, but the overall response rate (ORR), which was the main focus of the study, was similar in both arms, leading experts to believe that either drug could be useful in this setting.
Nearly 600 participants were given either drug with the chemotherapy regimen FOLFIRI. Participants' ORR was comparable, as was progression-free survival (PFS) at around 10 months. Overall survival was 28.7 months in the Erbitux arm compared with 25 months in the Avastin group.
"It's perplexing, in fact, why you would see the improved overall survival in the absence of a benefit in response rate or PFS, particularly given the apparent similar time on therapy," said Emily K. Bergsland, a gastrointestinal oncology specialist at the University of California, San Francisco, who led the discussion of the abstract after the presentation. While an answer wasn't available, it may have been because participants had different post-progression therapy, different reasons for treatment discontinuation, and perhaps there was a lack of correlation between PFS and survival in targeted therapies, she theorized.
Experts noted the drugs are also being studied in combination with FOLFOX, a more common chemotherapy regimen in the U.S. Results of that trial will be available later this year and may answer the question of which targeted agent would work best in U.S. populations. —Elizabeth Whittington
Disappointing results of a phase 3 study found that Avastin (bevacizumab) with chemoradiation did not prolong survival in patients with newly diagnosed glioblastoma, an aggressive, hard-to-treat brain tumor that has an average survival of fewer than 18 months. Avastin received accelerated approval for treatment of recurrent glioblastoma in 2009 due to promising phase 2 studies that showed the drug reduced tumor size in some patients. Based on those results and the lack of available options, Avastin is sometimes used to treat patients with newly diagnosed tumors in the hopes that it can be effective in this patient population. However, this latest study found the drug conveyed no overall survival or progression-free survival benefits and also increased side effects. Results from this trial and a similar international trial will continue to be analyzed to learn if there is a subset of patients who can still benefit. Avastin remains a viable option for patients who have progressed on previous treatments. —Elizabeth Whittington
Earlier data from a large, randomized clinical trial that investigated adding Avastin (bevacizumab) to standard chemotherapy for cervical cancer patients has been validated and may result in an additional treatment option for women with recurrent or advanced disease.
In the trial, 452 women with a recurrence of metastatic cervical cancer were randomized into one of four treatment groups to test standard chemotherapy (cisplatin and paclitaxel or topotecan and paclitaxel) with or without Avastin. The overall median survival for participants who received Avastin was 17 months versus 13.3 months for those who received chemotherapy alone. Moreover, participants taking Avastin experienced greater tumor shrinkage and longer response times.
Unlike many solid tumors, advanced cervical cancer doesn't respond well to the standard chemotherapy treatment. Adding the targeted biologic drug Avastin to standard chemotherapy could prolong survival in these patients by almost four months. Avastin works by blocking the blood supply that fuels tumor growth.
Cervical cancer is rare in the U.S., with about 12,000 new cases of invasive disease diagnosed annually. Yet, approximately 4,000 American women die of the disease every year. Worldwide, cervical cancer accounts for about a half-million new diagnoses annually and about 250,000 deaths. The disease can be caused by the human papillomavirus (HPV), making it not only unique among cancer types but also, with successful vaccines, a preventable illness. —Jon Garinn
When breast cancer cells are detected in the sentinel lymph node (the first node cancer might spread to from the tumor), current guidelines recommend the remainder of the nodes in the armpit be removed to stop the cancer's spread.
In a phase 3 international study, called AMAROS, participants with early-stage breast cancer and positive sentinel lymph nodes were randomly assigned to surgical removal of nodes or radiation. Results showed no significant differences in the two groups regarding survival or local recurrence but revealed substantial differences in the rates of lymphedema (a buildup of fluid). Of the women who had surgery, some 40 percent developed lymphedema after a year compared with about 22 percent in the radiation group. At five years, 28 percent of women in the surgery group experienced lymphedema versus 14 percent in the radiation group.
Lead investigator Emiel Rutgers from the Netherlands Cancer Institute in Amsterdam said the researchers would continue to follow the women for late effects of radiation. —Kathy LaTour
The optimal radiation dose for treating lung cancer was established more than 30 years ago, but improved technology has led some radiation oncologists to experiment with higher doses. The results of a phase 3 trial comparing standard dose (SD) radiation with high-dose (HD) radiation indicate that less is more, at least in terms of controlling the disease and prolonging survival.
In the study, 464 participants with stage 3 non-small cell lung cancer were randomized to receive either SD or HD concurrently with chemotherapy (paclitaxel and carboplatin). Additionally, participants in both arms were randomized to receive Erbitux (cetuximab), but data on that aspect of the study is not yet available. The median survival for participants in the SD arm was more than nine months longer compared with participants in the HD arm. Moreover, recurrence rates were almost 10 percent higher among participants in the HD arm.
"This really should put an end to higher dose treatment," said Sandra M. Swain, ASCO president. —Jon Garinn