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 June 1 to 5, attracting more than 31,000 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_2012.
The investigational breast cancer drug T-DM1 had a sputtering start when the Food and Drug Administration refused to grant it accelerated approval in 2010, even with promising phase 2 data. As the ASCO headliner this year, though, it appears new data from the large phase 3 trial, called EMILIA, will be enough to gain approval and make it available to metastatic HER2-positive breast cancer patients soon.
T-DM1 is one of a reformulated class of drugs called antibody-drug conjugates. It fuses together the Herceptin antibody (trastuzumab) to a potent drug called emtansine, packing a powerful punch to cancers that are fueled by overexpression of the HER2 receptor—even in patients whose cancers have progressed with Herceptin. Emtansine’s potency is at least 100 times more powerful than paclitaxel, and administration without severe side effects has been a challenge until now. Linking it to Herceptin, which delivers it directly to the cancer cell, reduces those side effects.
In the EMILIA trial, researchers followed 978 women whose cancer had progressed on a taxane and Herceptin. The women were given either an infusion of T-DM1 three times a week or the standard treatment of Xeloda (capecitabine) and Tykerb (lapatinib). After two years, researchers found that women in the investigational arm lived longer without disease progression (9.6 months compared with 6.4 months with standard therapy) and had fewer treatment-related side effects. There also appears to be a survival advantage, but researchers are waiting for data to mature before they can confirm that T-DM1 prolongs life. At the two-year follow-up, 65.4 percent of patients on T-DM1 were alive compared with 47.5 percent on the standard treatment.
Although the EMILIA trial tested T-DM1 alone, there are clinical trials combining T-DM1 with approved and other investigational drugs, such as pertuzumab, which was granted priority review earlier this year. Data from the EMILIA trial will be submitted to the FDA later this year for possible approval in metastatic, HER2-positive breast cancer. —Elizabeth Whittington
A new drug regimen that combines Treanda (bendamustine) and Rituxan (rituximab) has been shown to more than double progression-free survival time in patients with slow-growing and mantle cell lymphomas compared with standard chemotherapy, according to a German study of 514 patients.
The new regimen, which is based on a drug that has been used for decades in Europe and has been available in the U.S. since 2008, is not only more effective but also less toxic, according to researchers. In the study, patients with previously untreated indolent non-Hodgkin or mantle cell lymphomas were randomly assigned to receive the new regimen or standard chemotherapy, called Rituxan-CHOP (cyclophosphamide, Adriamycin [doxorubicin], vincristine and prednisone). Results indicated progression-free survival of nearly six years in the Treanda-Rituxan group compared with 2.6 years in the standard chemotherapy group. Side effects included mild skin reactions. —Jon Garinn
Although most cases of ovarian cancer respond to paclitaxel or other platinum-based chemotherapies, about 20 percent of cancers continue to progress with initial treatment while other cases later become resistant. To tackle these platinum-resistant cancers, a French research group examined adding Avastin (bevacizumab), which cuts off the blood supply to growing tumors, to standard chemotherapy in women whose cancers progressed within six months of their final dose of platinum therapy.
Participants were given either paclitaxel, Doxil (liposomal doxorubicin) or topotecan, depending on the physician’s choice of treatment, while half also received Avastin. After about a year of follow-up, researchers found Avastin significantly delayed time to disease progression. Median time of survival without the disease progressing was 6.7 months with Avastin compared with 3.4 months without. The benefit was seen across all subgroups, including age, size of tumor and type of chemotherapy. Although Avastin appeared to work well against this subset of ovarian cancer, it also increased side effects, including high blood pressure, proteinuria (abnormal amount of protein found in urine) and rare cases of perforations in the intestines. Overall survival data are expected in 2013.
The drug’s maker may be proceeding cautiously before submitting Avastin in ovarian cancer to the FDA. Avastin’s approval in metastatic breast cancer was revoked last year after a follow-up trial found that the drug did not prolong survival but added side effects. —EW
Results from a phase 3 international trial showed that the targeted drug afatinib significantly improves progression-free survival among patients with advanced lung cancer that harbors certain genetic mutations compared with standard chemotherapy.
Researchers randomly assigned 345 patients with epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma, a subtype of non-small cell lung cancer, to either afatinib or a chemotherapy regimen of Alimta (pemetrexed) and cisplatin.
Afatinib was shown to delay disease progression by more than four months compared with chemotherapy. Patients on afatinib had 11.1 months of progression-free survival versus 6.9 months experienced by patients on the chemotherapy regimen. In a group of patients with the most common types of EGFR mutations, progression-free survival was double that of standard therapy (13.6 months versus 6.9 months).
Studies have shown that afatinib inactivates the EGFR pathway longer than other EGFR-targeted therapies, such as Iressa (gefitinib) and Tarceva (erlotinib). Afatinib blocks the broader HER family of receptors, including HER2 and HER4.
Researchers also found that patients on afatinib experienced better quality of life. Afatinib is taken orally, which, according to the study’s lead author James Chih-Hsin Yang, MD, PhD, of the National Taiwan University Hospital, may require fewer visits to the doctor’s office as compared with the intravenous chemotherapy regimen. Also, the worsening of common lung cancer-related symptoms, such as coughing and shortness of breath, was delayed for those on afatinib compared with those receiving chemotherapy. Common side effects of afatinib included diarrhea, rash and mouth sores. —Katherine Lagomarsino
T??wo new targeted therapies, which each focus on a different way to block cancer growth signaling, delayed disease progression in patients with advanced, BRAF-mutated melanoma, according to results from separate phase 3 trials.
The METRIC study is the first phase 3 trial to evaluate the efficacy of trametinib, which blocks a protein that’s part of the BRAF signaling pathway. Patients who took trametinib experienced a median progression-free survival of 4.8 months versus 1.5 months for patients on dacarbazine or paclitaxel.
The BREAK-3 study found that dabrafenib, which acts against the mutated BRAF protein, extended median progression-free survival in comparison with dacarbazine: 5.1 months versus 2.7 months.
Currently, Zelboraf (vemurafenib), another BRAF inhibitor, is the only approved targeted therapy for the treatment of advanced melanoma, although many patients’ cancers eventually develop resistance to it or have serious side effects. A small phase 1 trial, which combines the two experimental therapies, has found a trend toward delaying disease progression. —KL
Patients who experience chemotherapy-induced peripheral neuropathy (CIPN), an often painful side effect that can involve numbness and tingling in the hands and feet, may find relief with the antidepressant Cymbalta (duloxetine), according to results from a phase 3 study. Although currently approved for the treatment of diabetic peripheral neuropathic pain, Cymbalta is the first drug that has proven effective in treating CIPN.
Experienced by about one-third of patients treated with taxanes and platinum-based chemotherapy, CIPN can develop weeks, months or years after treatment. Symptoms generally resolve completely, although healing of damaged nerves can take a few weeks to many months or even years.
In the study, 231 patients who had previously reported high levels of pain from CIPN were randomized to one of two arms. Participants in Arm A received Cymbalta for five weeks. After a one-week “washout” period, they received a placebo for five weeks. Participants in Arm B did the opposite, beginning with a placebo and ending with Cymbalta. Researchers reported a statistically significant decrease in pain for those taking Cymbalta in the initial treatment period. The most common side effect was fatigue.
Unfortunately, the drug didn’t work for everyone, which presents the next challenge, says lead investigator Ellen Lavoie Smith, PhD, of the University of Michigan School of Nursing. “We’ll try to identify who will respond so we can target this drug to those who are most likely to benefit.” —JG
In an international phase 3 trial, men with metastatic prostate cancer lived longer with continuous hormone therapy compared with intermittent therapy (5.8 years compared with 5.1 years). However, men with minimal metastases had a great benefit—nearly a two-year survival advantage.
The trial included more than 1,500 men with hormone-sensitive metastatic prostate cancer who were randomly assigned to receive intermittent or continuous hormone therapy. Prostate cancer can be fueled by androgens, such as testosterone, so hormone therapy is used to disrupt androgen production and stop the cancer’s growth. But because of the side effects of hormone therapy, which include reduced sexual drive and potency, hot flashes and weight gain, some doctors recommend intermittent treatment.
This new study shows that, despite the side effects, continuous treatment is more effective in men with less disease spread and comparably effective for those with more metastases. —JG
Patients with GIST, a rare gastrointestinal sarcoma, benefited from major advancements in chronic myelogenous leukemia when Gleevec (imatinib) revolutionized therapy for both cancers a decade ago. Now, an experimental drug in metastatic colorectal cancer may have the same effect. Regorafenib, which targets two cancer cell pathways, extended survival in both cancers in two separate studies.
In the GIST study, progression-free survival was extended from less than one month on placebo to 4.8 months on regorafenib. Patients in the placebo group whose cancers progressed were allowed to receive regorafenib. Because patients were allowed to cross over from the placebo group to regorafenib, the trial did not produce a statistically significant overall survival difference; however, researchers noted a trend for longer survival with regorafenib.
In the CORRECT trial, patients with colorectal cancer who received regorafenib also saw an improvement in median overall survival (6.4 months versus 5 months). —EW