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Endocrine therapy for breast cancer prevention in high-risk postmenopausal women

The US Preventive Services Task Force (USPSTF) and the American Society of Clinical Oncology (ASCO) have issued updated guidelines on the use of endocrine therapy as primary prevention in women at high risk for developing breast cancer [1,2]. For postmenopausal women, both guidelines now include selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) as preventive options, the latter being a new addition to the USPSTF guidelines. The USPSTF based its recommendations on a systematic review including two trials conducted in high-risk postmenopausal women, in which AIs resulted in an approximate 50 percent risk reduction for invasive breast cancer compared with placebo [3]. We agree with the USPSTF and ASCO guidelines regarding the use of endocrine therapy for postmenopausal women at high risk for developing breast cancer.


First-line nivolumab versus sorafenib for advanced hepatocellular cancer

The immune checkpoint inhibitor nivolumab is approved for treatment of advanced hepatocellular cancer (HCC) after prior treatment with sorafenib. In the phase III CheckMate 459 trial comparing nivolumab with sorafenib as initial therapy for patients with advanced HCC, progression-free and overall survival rates were similar, but the nivolumab group had a twofold higher objective response rate, more complete responses, fewer severe adverse events, and a lower likelihood of discontinuing therapy because of side effects [4]. Pending additional data and approval as a first-line agent, nivolumab might be offered as initial treatment to selected individuals with extensive disease burden or severe symptoms.


Cryotherapy versus LEEP for treatment of CIN in women with HIV

Data on the comparative efficacy of cryotherapy versus loop electrosurgical excision procedure (LEEP) for treatment of high-grade cervical intraepithelial neoplasia (CIN) in women with HIV are sparse. In a recent randomized trial comparing the efficacy of the procedures in 400 women in Kenya with HIV and CIN 2/3, cryotherapy resulted in a higher rate of recurrence over two years (30 versus 19 percent) [5]. Although these findings favor LEEP, we believe that both techniques remain acceptable pending more formal economic analysis and consideration of local-regional resources.


Complete lymph node dissection versus observation for positive sentinel lymph node biopsy in melanoma

For patients with cutaneous melanoma of the trunk or extremities and a positive sentinel lymph node biopsy (pSLNB), two randomized trials with intermediate follow-up found that routine immediate completion lymph node dissection (CLND) did not improve prognosis. In the final analysis of one of these trials (DeCOG-SLT), survival rates (distant metastasis-free survival, relapse-free survival, and overall survival) remained similar for the CLND and observation groups at five years, although CLND resulted in a trend toward fewer regional lymph node recurrences (11 versus 16 percent) [6]. These long-term data support current recommendations for observation with serial ultrasound examinations following pSLNB. Delayed CLND is performed in patients with confirmed lymph node recurrence.


Durvalumab plus platinum/etoposide in extensive-stage SCLC

For patients with newly diagnosed, extensive-stage (ES) small cell lung cancer (SCLC), previous data have shown improved survival with the addition of the anti-PD-L1 antibody atezolizumab to carboplatin and etoposide. Now, in a randomized trial including over 500 patients with chemotherapy-naive ES-SCLC, the anti-PD-L1 antibody durvalumab plus platinum/etoposide chemotherapy improved survival relative to chemotherapy alone (13 versus 10 months) [7]. Grade >=3 toxicity occurred in approximately 60 percent. The survival benefit and rates of toxicities with the addition of durvalumab are comparable to those previously observed with atezolizumab. For patients with newly diagnosed ES-SCLC, we recommend the addition of either atezolizumab or durvalumab to platinum/etoposide chemotherapy.


1. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Medication Use to Reduce Risk of Breast Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2019; 322:857.


2. Visvanathan K, Fabian CJ, Bantug E, et al. Use of Endocrine Therapy for Breast Cancer Risk Reduction: ASCO Clinical Practice Guideline Update. J Clin Oncol 2019; 37:3152.


3. Nelson HD, Fu R, Zakher B, et al. Medication Use for the Risk Reduction of Primary Breast Cancer in Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2019; 322:868.


4. Yau T, et al. LBA38_PR - CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Data presented at the 2019 meeting of the European Society for Medical Oncology (ESMO), September 27-October 1, 2019, Barcelona, Spain. Abstract available online at (Accessed on October 04, 2019).


5. Greene SA, De Vuyst H, John-Stewart GC, et al. Effect of Cryotherapy vs Loop Electrosurgical Excision Procedure on Cervical Disease Recurrence Among Women With HIV and High-Grade Cervical Lesions in Kenya: A Randomized Clinical Trial. JAMA 2019; 322:1570.


6. Leiter U, Stadler R, Mauch C, et al. Final Analysis of DeCOG-SLT Trial: No Survival Benefit for Complete Lymph Node Dissection in Patients With Melanoma With Positive Sentinel Node. J Clin Oncol 2019; 37:3000.


7. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase 3 trial. Lancet 2019.


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