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Mammography Associated With Breast Cancer Overdiagnosis
A study examining data for women age 40 years and older from the Surveillance, Epidemiology, and End Results (SEER) database calculated size-specific breast cancer case fatality rates prior to and after the widespread adoption of mammography screening. The authors estimated that approximately 80 percent of cancers identified by screening would not have caused clinical symptoms. Moreover, the authors calculated that at least two-thirds of the reduction in mortality associated with large tumors may be attributed to improved cancer treatments rather than screening. While acknowledging that cancer overdiagnosis does occur, and that randomized trials demonstrating benefit of mammography were largely conducted prior to modern therapy and imaging, we continue to suggest breast cancer screening for women ages 50 to 74 years, with individualized decision making for those between the ages of 40 and 50 years, given that the overall burden of evidence suggests benefit to screening.
Proton Pump Inhibitors May Diminish Capecitabine Efficacy
Two recent studies suggest that proton pump inhibitors diminish the effectiveness of capecitabine in the treatment of colorectal and gastroesophageal cancer. It is hypothesized that higher gastric pH levels may inhibit dissolution and absorption of capecitabine. Patients who are receiving a capecitabine-containing regimen for adjuvant treatment of colon cancer or other malignancies should, when possible, avoid taking concurrent proton pump inhibitors.
Adjuvant Therapy Following Resection of Renal Cell Carcinoma
In a previous randomized trial, adjuvant therapy with antiangiogenic therapy failed to demonstrate any improvement in either progression-free or overall survival in patients with resected localized renal cell carcinoma. In the S-TRAC trial, sunitinib significantly increased progression-free survival compared with placebo; however, there was no difference in overall survival. Currently, there is no defined role for systemic adjuvant therapy following complete surgical resection of a renal cell carcinoma except in the context of a clinical trial.
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer
In a phase III trial, niraparib was compared with placebo in approximately 550 patients with platinum-sensitive, recurrent ovarian cancer, stratified by germline mutation status. Niraparib improved progression-free survival in all patient groups, although over a third experienced severe hematologic toxicity. In the absence of overall survival data, and given significant toxicity, the appropriate timeframe and strategy for further treatment (with niraparib as maintenance therapy, or with chemotherapy upon disease progression) is unclear. Niraparib remains investigational and should not be used outside of a clinical trial.
Checkpoint Inhibitor Immunotherapy in Head and Neck Cancer
The management of advanced squamous cell carcinoma of the head and neck that is refractory to platinum-based chemotherapy is difficult. Clinical trials with antibodies that target the programmed cell death 1 (PD-1) protein have demonstrated important clinical activity, and both pembrolizumab and nivolumab have now been approved by the US Food and Drug Administration (FDA) in this setting. Anti-PD-1 antibodies are the preferred approach for second-line therapy of metastatic or recurrent squamous cell carcinoma of the head and neck that has progressed after prior platinum-based chemotherapy.
Atezolizumab in Advanced Non-Small Cell Lung Cancer
Novel immunotherapies are playing an increasing role in the treatment of non-small cell lung cancer (NSCLC), particularly in patients who have progressed on chemotherapy. In a phase III trial enrolling approximately 1200 patients who had progressed on platinum-based chemotherapy, those randomly assigned to the PD-L1 antibody atezolizumab compared with docetaxel experienced an improvement in median overall survival (13.8 versus 9.6 months) with fewer side effects, regardless of PD-L1 expression or histology. These data support our approach of offering patients who have progressed on prior chemotherapy (and targeted therapy, for those with EGFR or ALK genetic alterations) salvage treatment with immunotherapy.