@article{91f0865c08114c9e874e12782e7a5d63,
title = "A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non–small cell lung cancer: Hoosier Cancer Research Network LUN 14-179",
abstract = "Background: Five-year overall survival (OS) for patients with unresectable stage III non–small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti–programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease. Methods: Patients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression-free survival (PFS) and OS. Results: The median follow-up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2-46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P <.0001). The median PFS was 18.7 months (95% CI, 12.4-33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1-, 2-, and 3-year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%). Conclusions: Consolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone.",
keywords = "immunotherapy, pembrolizumab, stage III non–small cell lung cancer (NSCLC)",
author = "Durm, {Greg A.} and Jabbour, {Salma K.} and Althouse, {Sandra K.} and Ziyue Liu and Sadiq, {Ahad A.} and Zon, {Robin T.} and Jalal, {Shadia I.} and Kloecker, {Goetz H.} and Williamson, {Michael J.} and Reckamp, {Karen L.} and Langdon, {Robert M.} and Kio, {Ebenezer A.} and Gentzler, {Ryan D.} and Adesunloye, {Bamidele A.} and Harb, {Wael A.} and Walling, {Radhika V.} and Titzer, {Michael L.} and Hanna, {Nasser H.}",
note = "Funding Information: Greg A. Durm reports grant funding for research from Merck, AstraZeneca, and Bristol-Myers Squibb. Salma K. Jabbour reports grants, personal fees, and nonfinancial support from Merck outside the submitted work. Goetz H. Kloecker reports working on advisory boards for/receiving honoraria from Bristol-Myers Squibb, Genentech, Lilly, Bayer, Merck, and AstraZeneca. Karen L. Reckamp reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Calithera, Genentech, Lilly, Loxo, Takeda, and Tesaro outside the submitted work. Ryan D. Gentzler reports personal fees from AstraZeneca, Pfizer, Targeted Oncology, OncLive, and Rockpointe CME and grants from Pfizer, Merck, Bristol-Myers Squibb, Takeda, Helsinn, and Jounce outside the submitted work. Nasser H. Hanna reports grants from Merck, Genentech, AstraZeneca, and Bristol-Myers Squibb and other from UpToDate and Beyond Spring during the conduct of the study. The other authors made no disclosures. This trial is an investigator-initiated trial and was funded by Merck & Co. The trial was an investigator-initiated trial written and developed by the principal investigator with input from co-investigators. The trial was conducted through the Hoosier Cancer Research Network and was funded by Merck & Co. The trial protocol and all amendments were approved by the appropriate regulatory committees at each participating site. All patients provided written, informed consent for participation in the trial. A data safety monitoring board performed interim safety analyses after the first 10 patients and throughout the trial. All the authors attested that the trial was conducted in accordance with the protocol and all its amendments and with Good Clinical Practice standards. All authors were given access to the data and participated in the writing, reviewing, or editing of the manuscript. The main portion of the manuscript was written by the first author. Funding Information: This trial is an investigator‐initiated trial and was funded by Merck & Co. Publisher Copyright: {\textcopyright} 2020 American Cancer Society",
year = "2020",
month = oct,
day = "1",
doi = "10.1002/cncr.33083",
language = "English (US)",
volume = "126",
pages = "4353--4361",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "19",
}