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Atezolizumab and Nab-Paclitaxel in Triple Negative Breast Cancer
Triple negative breast cancer (TNBC) is more immunogenic than other breast cancer subtypes and represents a promising target for immunotherapy. In the randomized IMpassion130 trial, including 900 patients with treatment-naive metastatic TNBC, the combination of the programmed cell death ligand (PD-L1) antibody atezolizumab and nab-paclitaxel improved progression-free survival (PFS) by 1.5 months compared with nab-paclitaxel alone; however, among those with PD-L1 expressing tumors, the combination improved both PFS (7.5 versus 5.0 months) and overall survival (25 versus 15.5 months). Although some UpToDate experts advocate PD-L1 testing and the addition of atezolizumab to nab-paclitaxel in PD-L1 expressing TNBC, all acknowledge that PD-L1 testing is neither routine nor standardized in breast cancer, and that further evidence and/or regulatory approval are needed before this becomes a standard approach.
Aspirin Combined With Proton Pump Inhibitor for Patients With Barrett's Esophagus
Epidemiologic data suggest that drugs that inhibit cyclooxygenase, such as aspirin, might prevent high-grade dysplasia and esophageal cancer in patients with Barrett's esophagus. In a recent trial, over 2,500 patients with Barrett's esophagus were randomly assigned to low or high-dose esomeprazole, with or without full-dose aspirin, and were followed for a median of nine years. Compared with low-dose proton pump inhibitor (PPI) alone, aspirin combined with high-dose PPI resulted in the longest time interval to a composite endpoint (all-cause mortality, esophageal carcinoma, or high-grade dysplasia). However, the difference in event rate between aspirin and no aspirin was relatively modest and not statistically significant, and it is uncertain whether low-dose aspirin (which many patients with Barrett's esophagus use for other indications) would have a similar effect. Given these uncertainties and the potential risks associated with high-dose PPIs, we do not routinely use full-dose aspirin combined with high-dose PPI for chemoprevention or increase the PPI dose beyond what is needed for symptom control and healing of reflux esophagitis.
Chemotherapy Backbone for HER2-Overexpressing Advanced Esophagogastric Cancer
For patients with advanced human epidermal growth factor receptor 2 (HER2)-overexpressing esophagogastric adenocarcinomas, the addition of trastuzumab to cisplatin plus a fluoropyrimidine significantly improved survival in the phase III ToGA trial, although the optimal chemotherapy backbone is not established. A meta-analysis comparing different first-line trastuzumab-containing regimens in 15 published studies concluded that survival was better and treatment was less toxic when trastuzumab was combined with oxaliplatin plus a fluoropyrimidine compared with cisplatin plus a fluoropyrimidine. For most patients receiving initial trastuzumab-containing chemotherapy, an oxaliplatin/fluoropyrimidine doublet is preferred over cisplatin/fluoropyrimidine.
Hypofractionated Radiation Therapy for Early Prostate Cancer
According to new guidelines from the American Society for Radiation Oncology, the American Society of Clinical Oncology, and the American Urological Association, men with early prostate cancer who choose external beam radiation therapy (RT) and who do not need nodal irradiation should be offered moderate hypofractionated (eg, 60 Gy in 20 fractions or 70 Gy in 28 fractions) rather than conventional fractionation RT (eg, 78 Gy in 39 fractions). Men should be counseled about the small increased risk of early gastrointestinal (GI) toxicity associated with this approach and the limited information on late GI and genitourinary toxicity beyond five years. Stereotactic body RT (ultrahypofractionation RT, eg, 42.7 Gy in seven fractions over 2.5 weeks) is an acceptable alternative for men with low- or intermediate-risk disease who do not need nodal irradiation, but not for high-risk disease.
Maintenance Olaparib in BRCA-Associated Advanced Ovarian Cancer
The role of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in advanced epithelial ovarian cancer (EOC) is under active investigation, particularly for those with BRCA-associated cancers. In the randomized phase III SOLO1 trial, olaparib for maintenance treatment was compared with placebo in almost 400 women with an identified BRCA mutation, advanced high-grade serous or endometrioid cancer, and a response to frontline platinum-based chemotherapy. More than 99 percent of the women had germline BRCA mutations. At a follow-up of 41 months, olaparib improved the three-year rate of freedom from disease progression or death (60 versus 27 percent). Given these data, we suggest maintenance olaparib for BRCA mutation carriers with advanced EOC who respond to frontline platinum-based therapy. Additionally, some UpToDate experts suggest that women with advanced EOC who do not have a BRCA germline mutation undergo tumor assessment for somatic BRCA mutations, as patients with these cancers may also derive benefit from maintenance olaparib.
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