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Pembrolizumab in Non-Small-Cell Lung Cancer


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vaginosis at baseline (39% vs. 21%, P? =? 0.4 for interaction). A previous phase 1 trial3 did not show a loss of lactobacillus species as a result of the dapivirine ring, and we found no clinical evidence of genital tract toxicity in our trial. Seidman et al. note, correctly, that the dapivirine vaginal ring is unlikely to provide substantial protection from HIV-1 in nonvaginal HIV-1 exposures such as anal sex. In our trial, a minority of participants reported engaging in anal sex. During the 3 months before enrollment, in an in-person interview, 2% of the participants reported having any anal sex, and among participants who completed an interview through an audio computer–assisted system, 13% reported having any anal sex. Among the participants who reported having any anal sex, most reported less than one act per month and fewer than 10% reported more than three acts per month. Vaginal sex is responsible for most new infections in African women. Nevertheless, among individual women, the risk of HIV-1 associated with anal, intravenous, and other exposures may be par-

ticularly important. As Seidman et al. indicate, the results of our study may facilitate expansion of HIV prevention options in women. Jared?M. Baeten, M.D., Ph.D.
University of Washington Seattle, WA jbaeten@??uw?.?edu

Elizabeth?R. Brown, Sc.D.
Fred Hutchinson Cancer Research Center Seattle, WA

Sharon?L. Hillier, Ph.D.
University of Pittsburgh Pittsburgh, PA Since publication of their article, the authors report no further potential conflict of interest.
1. Low N, Chersich MF, Schmidlin K, et al. Intravaginal prac-

tices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis. PLoS Med 2011;? 8(2):? e1000416. 2. Clarke JG, Peipert JF, Hillier SL, et al. Microflora changes with the use of a vaginal microbicide. Sex Transm Dis 2002;? 29:? 288-93. 3. Chen BA, Panther L, Marzinke MA, et al. Phase 1 safety, pharmacokinetics, and pharmacodynamics of dapivirine and maraviroc vaginal rings: a double-blind randomized trial. J Acquir Immune Defic Syndr 2015;? 70:? 242-9.
DOI: 10.1056/NEJMc1616546

Pembrolizumab in Non–Small-Cell Lung Cancer
To the Editor: Reck et al. (Nov. 10 issue)1 found that the efficacy of pembrolizumab was superior to that of chemotherapy (including carboplatin– paclitaxel) as first-line therapy in patients with metastatic programmed death 1 ligand (PD-L1)– overexpressing non–small-cell lung cancers (NSCLCs) that do not have epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK ) molecular abnormalities. The standard regimen choices did not include carbo? platin–paclitaxel–bevacizumab or carboplatin– albumin-bound paclitaxel (nab-paclitaxel). Carboplatin–paclitaxel–bevacizumab has been associated with longer overall survival than carboplatin–paclitaxel in patients with non– squamous-cell NSCLC.2 This combination therapy has been endorsed by the National Comprehensive Cancer Network (NCCN) as a category 1 therapy and approved by the Food and Drug Administration (FDA) as first-line therapy for metastatic NSCLC.3 Reck et al. conclude that the efficacy of pembrolizumab in the 29 patients with squamouscell cancer was “notable.” However, in a recent

large trial involving patients with either squamous-cell NSCLC or non–squamous-cell NSCLC, the higher rate of response that was observed with carboplatin–nab-paclitaxel than with carboplatin–paclitaxel resulted in the FDA approval and NCCN category 1 endorsement of carboplatin–nab-paclitaxel as first-line therapy for metastatic NSCLC.3 The response rate among patients with squamous-cell cancer was 41% with carboplatin–nab-paclitaxel.4 Studies comparing the efficacy of carboplatin–paclitaxel–bevacizumab or carboplatin–nab-paclitaxel with pembrolizu? mab will further clarify the role of pembroliz? umab in the treatment of metastatic NSCLC. Steven Sorscher, M.D.
Wake Forest School of Medicine Winston-Salem, NC Dr. Sorscher reports receiving speaking fees from Pfizer, Celgene, Genentech, and Eli Lilly. No other potential conflict of interest relevant to this letter was reported.
1. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembroli-

zumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med 2016;? 375:? 1823-33. 2. Sandler A, Gray R, Perry MC, et al. Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. N Engl J Med 2006;?355:?2542-50.

n engl j med 376;10?nejm.org? March 9, 2017


lines in oncology — non-small cell lung cancer, version 1. Port Washington, PA:?National Comprehensive Cancer Network, 2017 (https:/?/?w ww?.nccn?.org/?professionals/?physician_gls/?f_guidelines? .asp). 4. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nabpaclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 2012;? 30:? 2055-62.
DOI: 10.1056/NEJMc1615559

3. Ettinger D, Wood DE, Aisner DL, et al. NCCN practice guide-

The authors reply: The standard regimen choices in the KEYNOTE-024 trial did not include bevacizumab or nab-paclitaxel. The permitted combinations represent a standard of care in patients with advanced NSCLC worldwide. We Martin Reck, M.D., Ph.D. do not believe that the addition of bevacizumab German Center of Lung Research or nab-paclitaxel would affect the outcomes be- Grosshansdorf, Germany cause of several factors. First, a very small num- Julie?R. Brahmer, M.D. ber of patients received a paclitaxel combination Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (17 of 150 patients randomly assigned to chemo- Baltimore, MD therapy). Second, although a carboplatin–nabSince publication of their article, the authors report no further paclitaxel regimen has shown a higher rate of potential conflict of interest. response than carboplatin–paclitaxel, it did not 1. Socinski MA, Okamoto I, Hon JK, et al. Safety and efficacy result in longer survival, even among patients analysis by histology of weekly nab-paclitaxel in combination with squamous-cell carcinoma (hazard ratio for with carboplatin as first-line therapy in patients with advanced 24:? 2390-6. death, 0.89; 95% confidence interval, 0.72 to 1.10; non-small-cell lung cancer. Ann Oncol 2013;? 1 P?=?0.28). Third, the introduction of bevacizumab DOI: 10.1056/NEJMc1615559

in combination with carboplatin–paclitaxel would have required the introduction of an additional selection factor related to the restricted eligibility criteria for bevacizumab use. Decisions regarding which contemporary standard therapies to include in lung-cancer trials have become more complex. Issues arise particularly when there are differences with regard to preferred standard therapy across the globe. In this trial, patterns of care show that pemetrexedbased therapy remains a preferred standard for non–squamous-cell histologic type NSCLC and gemcitabine-based therapy remains preferred for squamous-cell histologic type NSCLC.

Abdominal Aortic Aneurysm Repair in England and the United States
To the Editor: Karthikesalingam et al. (Nov. 24 issue)1 found a larger diameter of abdominal aortic aneurysm at the time of repair in England than in the United States (mean diameter, 63.8 vs. 58.2 mm), as well as higher rates of hospitalization due to aneurysm rupture (odds ratio, 2.23; P<0.001) and aneurysm-related death (odds ratio, 3.60; P<0.001). As the authors mention, we previously suggested that the size threshold for aneurysm repair should be revisited in the era of endovascular repair.2 As the authors correctly state, “The decision about whether to repair an abdominal aortic aneurysm requires consideration of a balance of risks, including aneurysm rupture if surgery is not performed and death due to aneurysm repair itself.” Endovascular aneurysm repair is associated with lower mortality rates than open repair.3-5 As a consequence, the balance of risks (risk of aneurysm rupture vs. risk of death due to aneurysm repair) shifts toward a lower size threshold for repair.2 The current study provides the appropriate evidence. Why do the authors think we “would require new clinical trials,” and how realistic is it to expect new randomized, controlled trials to answer this question? Kosmas?I. Paraskevas, M.D., Ph.D.
Freeman Hospital Newcastle-upon-Tyne, United Kingdom paraskevask@??hotmail?.?com

Dimitri?P. Mikhailidis, M.D.
University College London London, United Kingdom No potential conflict of interest relevant to this letter was reported.
1. Karthikesalingam A, Vidal-Diez A, Holt PJ, et al. Thresholds for abdominal aortic aneurysm repair in England and the United States. N Engl J Med 2016;? 375:? 2051-9.

n engl j med 376;10?nejm.org? March 9, 2017


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