ASCO Highlights: Novel heat shock protein 90 inhibitor ganetespib improves survival in advanced lung cancer

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Survey data show cancer drug shortages persist, doctors adapting in different ways

A survey of 250 U.S. oncologists and hematologists finds that more than 80 percent of cancer doctors encountered cancer drug shortages between March and September of 2012, and many reported that shortages affected the quality of patient care that doctors were able to provide. The study also found that the cost of care was also driven upward as physicians are forced to substitute more expensive drugs for cheaper generics. Shortages have also interfered with patient participation in clinical trials, slowing the pace of research progress. These findings were echoed by a second survey, conducted by the American Society of Clinical Oncology.

Two common adjuvant chemotherapy regimens have comparable efficacy but differ in side effects

A phase III randomized clinical trial finds that low-dose weekly administration of paclitaxel (Taxol) and standard dose, every two weeks administration result in equal progression-free survival for women with higher-risk early-stage breast cancer who have undergone surgery. However, researchers found that certain side effects were more common with the every two weeks regimen, suggesting the weekly schedule may be preferable. These findings may lead to more doctors utilizing the weekly schedule, which could also result in cost savings, as the every two weeks regimen requires additional supportive care, including growth factors (e.g., pegfilgrastim) to boost white blood cell production.

The estimated five-year progression-free survival rates for weekly and every two weeks paclitaxel were equivalent – 82 percent and 81 percent, respectively. The two schedules differed in the type and severity of side effects: the every two week schedule was associated with higher frequency of allergic reactions (1.4 percent vs. 0.6 percent), and muscle and bone pain (11 percent vs. 3 percent), compared to the weekly schedule. The frequency of neurologic toxicity, a common side effect involving numbness, tingling and pain of the fingers and toes, was also higher in the every two week regimen (17 percent vs. 10 percent), but this difference may have been smaller had the patients received only four cycles of every two weeks therapy (as is current practice) rather than six. (Six cycles of every two weeks regimen was selected in this study so that patients in both arms would be on treatment for 12 weeks).

Axillary radiotherapy is a safe alternative to axillary lymph node surgery, can reduce risk of lymphedema

The drugs that were most commonly reported in shortage were leucovorin, liposomal doxorubicin, 5-fluorouracil, bleomycin, and cytarabine. These drugs are commonly used in the treatment of various forms of cancer, including gastrointestinal, blood (leukemia, lymphoma, myeloma), breast, ovarian and testicular cancers. Cytarabine is particularly critical for curing certain forms of acute leukemia. When asked about the impact of cancer drug shortages over the prior 6 months, 94 percent reported that their patients‟ treatment was affected and 83 percent were unable to provide standard chemotherapy. About 13 percent of respondents reported that shortages prevented patient enrollment or suspended participation in clinical trials.A European phase III clinical trial, called AMAROS, found that axillary radiotherapy (ART) and lymph node surgery (axillary lymph node dissection, ALND) result in equivalent overall and disease-free survival at five years after treatment for women with sentinel lymph node positive early breast cancer. However, a debilitating side effect known as lymphedema was twice as common among women who underwent surgery.

Many African American women with early-onset or triple negative breast cancer have inherited mutations in breast cancer-related genes

A genomic profiling study of African American women with breast cancer referred for genetic counseling at The University of Chicago finds that about one in five carries an inherited abnormality in at least one of 18 genes associated with breast cancer susceptibility. Such mutations were more prevalent among women with aggressive triple negative breast cancer, early onset disease, and a family history of breast and ovarian cancer. The findings suggest that broader genetic screening may be beneficial for these women and their family members.

Genomic DNA from 249 unrelated African American women with breast cancer was analyzed for the presence of mutations in 18 breast cancer susceptibility genes using an assay called BROCA, which utilizes new tools called targeted genomic capture and next generation sequencing. Overall, 56 out of 249 patients (22 percent) had at least one clinically relevant mutation. Most of these women carried a single mutation.

First-in-class targeted drug improves survival for patients with advanced lung cancer

The five-year breast cancer recurrence rates in the axillary nodes were very low overall – 0.54 percent and 1.03 percent in the ALND and ART groups, respectively. There were no significant differences between the two treatment groups regarding the estimated five-year overall survival (92.5-93.3 percent) and disease-free survival rates (82.6-86.9 percent). In contrast, there were striking differences in the numbers of patients who experienced lymphedema. In the first year, 40 percent of patients in the ALND arm had lymphedema compared to 22 percent in the ART arm. In subsequent years, the number of patients with lymphedema decreased, but the trend persisted: at five years the rates were 28 percent and 14 percent.A large randomized phase II study, GALAXY-1, finds that a novel heat shock protein (Hsp) 90 inhibitor, ganetespib, when combined with docetaxel in second-line (salvage) therapy, leads to longer overall survival compared to standard second-line docetaxel alone in patients with advanced lung adenocarcinoma that progresses after initial therapy. If confirmed in an ongoing phase III trial, this would be the first treatment to improve patient outcomes in this setting in a decade.