Hot Paper in Medicine

August 2014
“Safety, activity, and immune correlates of anti-PD-1 antibody in cancer,” by Suzanne L. Topalian, et al., New England Journal of Medicine, 366(26): 2443-54, 28 June 2012.

Abstract: “BACKGROUND Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. METHODS We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. RESULTS A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non-small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non-small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1-PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1-negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1-positive tumors had an objective response (P = 0.006). CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response.”

This 2012 report from the New England Journal of Medicine was cited 67 times in current journal articles indexed by Thomson Reuters during March-April 2014. Having registered as the second-most-cited paper in Medicine during the previous count for January-February, the report now ascends to the #1 spot, covering Medicine papers published in the last two years, aside from reviews. Prior to the most recent bimonthly count, citations to the report have accrued as follows, as tracked by Essential Science Indicators Hot Papers:

January-February 2014: 75 citations
November-December 2013: 69
September-October 2013: 72
July-August 2013: 70
May-June 2013: 68
March-April 2013: 70
January-February 2013: 61
November-December 2012: 34
September-October 2012: 18
July-August 2012: 5
May-June 2012: 7

Total citations to date: 616

SOURCE: Thomson Reuters Web of Science

The data and citation records included in this report are from Thomson Reuters Web of ScienceTM. Web of ScienceTM is a registered trademark of Thomson Reuters. All rights reserved.