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Ovarian Suppression With Either Tamoxifen or an Aromatase Inhibitor in Premenopausal Women With Early Breast Cancer
Two trials have examined the efficacy of ovarian suppression (OS) added to either adjuvant tamoxifen or the aromatase inhibitor exemestane in premenopausal women with early breast cancer. In the SOFT trial, compared with tamoxifen alone, OS plus tamoxifen improved eight-year disease-free survival rate (83 versus 79 percent), as did OS plus exemestane (86 percent). Women receiving OS experienced more musculoskeletal side effects, and for those receiving exemestane, higher rates of osteoporosis. Distant recurrence rates at eight years were lower for exemestane plus OS compared with tamoxifen plus OS in both trials. Given the greater toxicity associated with the addition of OS to other endocrine therapy, we suggest it for women with cancers at higher risk for relapse. For women with lower risk cancers, we suggest tamoxifen as single-agent therapy, although such women who prioritize minimizing breast cancer risks over side effects of treatment may also be appropriate candidates for OS with other endocrine therapy.
BRAF Inhibitor Plus Cetuximab for RAS Wild-Type BRAF V600E-Mutated Metastatic Colorectal Cancer
Mutations in the BRAF V600E gene are associated with resistance to agents targeting the epidermal growth factor receptor (EGFR) in metastatic colorectal cancer (mCRC). Whether resistance can be overcome through the use of a BRAF inhibitor was addressed in the randomized phase III BEACON trial in patients with RAS wild-type BRAF V600E mutant progressive mCRC that compared cetuximab plus the BRAF inhibitor encorafenib (with or without the MEK inhibitor binimetinib) versus cetuximab plus irinotecan. In a preliminary report of 30 patients who received encorafenib plus binimetinib and cetuximab during the safety lead-in of the trial, clinical activity was encouraging with an overall response rate of 41 percent, and at least one complete response. These results are consistent with previous findings supporting efficacy for a different BRAF inhibitor (vemurafenib) in combination with cetuximab and irinotecan compared with cetuximab and irinotecan alone in unresectable mCRC. Although the data are not robust, the combination of vemurafenib plus an anti-EGFR agent and irinotecan is a reasonable option for second-line therapy in patients who have RAS wild-type but BRAF V600E mutant mCRC.
Radiation Therapy for Lung Metastases in Children With Wilms Tumor
The optimal management for children with Wilms tumor with lung metastases is uncertain. Historically, most patients were treated with whole lung radiation therapy (RT). In a study of patients with favorable histology Wilms tumor and isolated lung metastases, use of lung RT was omitted if initial chemotherapy led to a complete lung nodule response. Overall and event-free survival were superior to previous studies in which all patients received lung RT. These results suggest that the strategy of tailoring RT to the patient's response to chemotherapy results in excellent outcomes and avoids long-term radiation-related toxicity in children with lung metastases.
Updated ACS Guidelines on Colorectal Cancer Screening
The American Cancer Society (ACS) has updated its colorectal cancer (CRC) screening guidelines. On the basis of an apparent increase in the incidence of CRC in younger adults, the ACS guidelines now make a "qualified" recommendation to begin screening persons at average risk for CRC at age 45 years, with a strong recommendation to screen at age 50 years and above. The guidelines also now offer six testing options to select among: colonoscopy every 10 years, computed tomographic colonography (CTC) every five years, sigmoidoscopy every five years, take-home high-sensitivity guaiac-based fecal occult blood testing yearly, take-home fecal immunochemical testing (FIT) yearly, and multitargeted stool-DNA test every three years, noting that any positive result on a noncolonoscopy test should be followed up with timely colonoscopy. In including more tests, rather than prioritizing tests that could detect both polyps and cancer, the ACS notes that screening with a test acceptable to the patient is preferable to the patient declining screening. For average-risk patients, and in keeping with most guidelines, we continue to initiate screening starting at age 50 years. We prefer colonoscopy when possible, and FIT or CTC if the patient cannot or will not have colonoscopy.
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