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Adjuvant Pertuzumab for HER2-Positive Breast Cancer

While pertuzumab has shown benefit in the neoadjuvant setting for high-risk HER2-positive breast cancer, its role in the adjuvant setting is just now emerging. In the phase III APHINITY trial, over 4800 patients with HER2-positive breast cancer who were treated with adjuvant chemotherapy and trastuzumab were randomly assigned to pertuzumab (concurrent with trastuzumab) or placebo. At a median follow-up of approximately 45 months, patients receiving pertuzumab had higher three-year invasive disease-free survival rates (94 versus 93 percent), with the greatest benefit for those with node-positive disease. Given this trial, we now suggest the addition of adjuvant pertuzumab for women with node-positive disease or larger, node-negative tumors (>2 cm). However, some patients may reasonably choose against additional treatment, given the added toxicities of pertuzumab and lack of demonstrated overall survival benefit.

Regorafenib for Second-Line Treatment of Advanced Hepatocellular Cancer

In a randomized trial, regorafenib was shown to provide benefit as a second-line agent for patients with advanced hepatocellular cancer (HCC) and Child-Pugh A liver function who progressed after receiving sorafenib. Compared with placebo, regorafenib significantly improved median overall survival, and the main toxicities were hypertension, hand-foot skin reaction, fatigue, and diarrhea. Largely based upon these data, in April 2017, the US Food and Drug Administration expanded the indications for regorafenib to include patients with HCC previously treated with sorafenib. While optimal patient selection has not been established, a trial of regorafenib is reasonable for patients progressing after first-line sorafenib who maintain a good performance status and adequate liver function, and who are willing to trade treatment-related morbidity for the possibility of a small gain in survival.

Postoperative Stereotactic Radiosurgery for Resected Brain Metastases

Two randomized trials lend further support to the use of postoperative stereotactic radiosurgery (SRS) rather than whole brain radiation therapy (WBRT) or observation after resection of a single brain metastasis. In one trial, patients treated with single-fraction SRS to the surgical cavity had improved neurocognitive function and similar overall survival compared with those treated with WBRT. In the second trial, single-fraction SRS decreased rates of local recurrence compared with observation, especially for tumors smaller than 2.5 cm preoperatively. Larger tumors may be better suited for multiple-fraction SRS, which allows for a higher dose of radiation to be delivered to the surgical cavity.

Durability of Pembrolizumab-Induced Remissions for Advanced Melanoma

In the previously reported phase III KEYNOTE-006 trial, pembrolizumab was compared with ipilimumab, with treatment continuing for up to two years in the absence of progression or toxicity. Results were updated at the 2017 American Society of Clinical Oncology meeting. Overall, 19 percent of responding patients completed the two years of planned treatment with pembrolizumab and discontinued therapy. With a median follow-up of 9.7 months after pembrolizumab discontinuation, 91 percent of patients remained progression free. These results provide additional support for the durability of responses to pembrolizumab and the ability to discontinue treatment after two years.

Oral Contraceptives and Ovarian Cancer Risk

Use of oral estrogen-progestin contraceptives is associated with a reduction in risk of ovarian cancer. In the largest and longest duration study of oral contraceptive use, the Royal College of General Practitioners' Oral Contraception Study followed over 46,000 women for up to 44 years and found that ever-use of oral contraceptives was associated with a 33 percent reduction in ovarian cancer risk. This finding supports previous data and our recommendation for use of oral contraceptives in women who desire ovarian cancer risk reduction who have not undergone risk reduction surgery and who are not trying to conceive.

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