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Adjuvant Trastuzumab in Early HER2-Positive Breast Cancer

In the Herceptin Adjuvant (HERA) trial, over 5000 women with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer who had completed adjuvant chemotherapy were randomly assigned to observation or to the addition of trastuzumab for one or two years. In the final report of this study, at a median of 11 years of follow-up, one year of trastuzumab improved disease-free and overall survival relative to observation. There were no further improvements with extension to two years of trastuzumab, but the incidence of cardiotoxicity was higher. These results support our approach of administering adjuvant trastuzumab for one year to those with HER2-positive early breast cancer.

Flexible Sigmoidoscopy and Colorectal Cancer Screening in Older Women

Flexible sigmoidoscopy is one of several screening modalities recommended by the US Preventive Services Task Force for colorectal cancer (CRC) screening. However, sigmoidoscopy is less effective at detecting lesions in the right side of the colon (beyond the 60 cm reach of the sigmoidoscope) than the left side, and right-sided lesions are more common in older women. A study that pooled results from three randomized trials (nearly 300,000 individuals) comparing screening by sigmoidoscopy with no screening found that the incidence of CRC at 10 to 12 years was decreased in men but, in women, only in those younger than 60 years. Current screening recommendations do not indicate gender-based preferences for screening options, but these findings call into question the effectiveness of flexible sigmoidoscopy as a screening modality for women over age 60 years.

Adjuvant Chemotherapy for Urothelial Carcinoma of the Upper Urinary Tract

Patients with locally advanced urothelial carcinoma of the upper urinary tract and those with positive lymph nodes following nephroureterectomy are at high risk for recurrence and death. A retrospective analysis of data from the National Cancer Database found that those receiving adjuvant chemotherapy had a significantly prolonged overall survival. In the absence of randomized trials, we suggest adjuvant chemotherapy for these patients if they are fit for chemotherapy.

Dosing Interval for Zoledronic Acid in Patients With Bone Metastases

For patients with bone metastases from a solid tumor, the approved dose and schedule of administration for zoledronic acid to reduce the frequency of skeletal-related events (SREs) is 4 mg every three to four weeks. Less frequent dosing is supported by data from CALGB (Alliance) trial 70604, which randomly assigned 1822 patients with bone metastases from breast or prostate cancer or multiple myeloma to the same dose of zoledronic acid every 4 or every 12 weeks for two years, starting with the first dose. There was no difference in the proportion of patients who developed at least one SRE (29.5 versus 28.6 percent). There are now sufficient data in breast and prostate cancer to support dosing of zoledronic acid every 12 rather than every 4 weeks, and we suggest this approach for most patients. We still prefer every-four-week dosing, at least initially, for patients who have extensive or highly symptomatic bone metastases.

Rucaparib in BRCA Mutation-Associated Advanced Ovarian Cancer

Poly-ADP ribose polymerase (PARP) inhibitors have activity against BRCA mutation-associated epithelial ovarian cancer. The PARP inhibitor rucaparib is now approved by the US Food and Drug Administration for BRCA mutation-associated advanced ovarian cancer that has been treated with two or more lines of chemotherapy, based on response rates of over 50 percent in such cancers. We now offer rucaparib as an option in this setting.

Screening Interval for Lung Cancer

The optimal strategy for screening high-risk individuals for lung cancer is the subject of active study. In new results from the NELSON trial, in which almost 16,000 current or former smokers were randomly assigned to low-dose computed tomography (LDCT)-based screening versus observation only, extending the screening interval from 1 to 2.5 years reduced the proportion of cancers detected at an early stage. These data support our approach to screen annually with LDCT when screening patients who are at high risk for lung cancer.