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A Nonanthracycline-Containing Adjuvant Regimen for HER2-Positive Breast Cancer
The efficacy and safety of combining trastuzumab with a nonanthracycline-containing chemotherapy regimen was evaluated in the Breast Cancer International Research Group 006 (BCIRG-006) trial of over 3200 women with HER2-positive and node-positive breast cancer or high-risk node-negative disease. A preliminary report of 10-year outcomes suggests that, compared with doxorubicin and cyclophosphamide followed by docetaxel (ACT), both ACT with trastuzumab (ACTH) as well as docetaxel, carboplatin, and trastuzumab (TCH) lead to improved disease-free survival (DFS, 75 and 73 percent, respectively, versus 68 percent for ACT) and overall survival (OS, 86 and 83 percent, respectively, versus 79 percent for ACT). A trend toward improved DFS and OS was seen for ACTH compared with TCH, but ACTH was associated with slightly greater toxicity. These results support our recommendation that TCH is an effective alternative treatment to ACTH as adjuvant therapy for HER2-positive breast cancer.
Denosumab in Early Breast Cancer
The anti-RANK-ligand denosumab, used concurrently with adjuvant aromatase inhibitors (AIs), is known to improve bone mineral density (BMD) and reduce the risk of fracture. Data are emerging regarding the potential for denosumab to improve disease-free survival (DFS) in postmenopausal women receiving AIs for breast cancer. The Austrian Breast and Colorectal Cancer Study Group (ABCSG-18) study ABCSG-18 assessed DFS in 3400 postmenopausal women on aromatase inhibitors for hormone receptor-positive breast cancer who were randomly assigned to denosumab or placebo. In preliminary data, at a median follow-up of four years, a trend towards improved DFS was seen in the denosumab group. In subset analyses, benefit from denosumab was observed in women with tumors that were larger than 2 cm, that were both estrogen receptor (ER)-positive and progesterone receptor (PR)-positive, or that had ductal histology. We await final reporting of data from ABCSG-18, as well as the Denosumab as Adjuvant Treatment for Women With High Risk Early Breast Cancer Receiving Neoadjuvant or Adjuvant Therapy (D-CARE) study (NCT01077154), to provide further information regarding potential anti-cancer benefits of this agent.
Screening for Ovarian Cancer in Average Risk Women
The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is the largest randomized trial evaluating the use of serum testing for CA 125 and transvaginal ultrasound (TVUS) for ovarian cancer screening in average risk women. The trial compared three arms: no screening; screening with annual transvaginal ultrasound; and multimodal screening (MMS, consisting of annual CA 125 testing, followed by TVUS if the CA 125 was abnormal, using an algorithmic guideline). After a median of 11 years, cancers were detected in 0.7 percent of women in the MMS group and 0.6 percent of women in the control and TVUS-only groups. Compared with no screening, MMS detected cancer at an earlier stage and the primary analysis showed a nonsignificant trend toward a 15 percent reduction (95% CI -3 to 30) in mortality from ovarian cancer for MMS. When prevalent ovarian cancer cases were excluded, the mortality reduction with MMS was significant. The results of the UKCTOCS trial are not consistent with results from another randomized trial that did not show decreased mortality with MMS. Based on the available data, it is not clear that the benefits of screening for ovarian cancer outweigh the harms related to the adverse effects associated with false positive findings. UpToDate(R) suggests not screening average risk women for ovarian cancer.
Updated Guidelines for Endoscopic Surveillance After Treatment of Colorectal Cancer
Updated guidelines for posttreatment endoscopic surveillance from a United States Multi-Society Task Force on Colorectal Cancer are available. The most notable change is a recommendation for flexible sigmoidoscopy or endoscopic ultrasound every three to six months for the first two to three years after surgery for rectal cancer in patients who are at increased risk for a local recurrence, including those with localized rectal cancer who have undergone surgery without total mesorectal excision (TME), those who have undergone transanal local excision or endoscopic submucosal dissection alone, and those with locally advanced rectal cancer who did not receive neoadjuvant chemoradiotherapy followed by TME.
Adjuvant VEGF Inhibitors Not Beneficial for Completely Resected Renal Cell Carcinoma
Anti-angiogenic agents targeting the vascular endothelial growth factor (VEGF) pathway can prolong overall survival in patients with metastatic clear cell renal cell carcinoma (RCC), and this observation has led to their evaluation as adjuvant therapy. In the ASSURE trial, patients with completely resected RCC were randomly assigned to sunitinib, sorafenib, or placebo. There was no improvement in disease-free survival, the primary endpoint of the trial, with either agent, and treatment was associated with a significant increase in serious toxicity with both agents. There is currently no role for adjuvant therapy using these agents after a complete resection of RCC. The use of adjuvant systemic therapy should be limited to formal clinical trials.