title: Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.
abstract: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA.
  
  
  
  We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169.
  
  
  
  We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported.
  
  
  
  To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease.
  
  
  
  National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Van K
authors.initials: VK
authors.lastname: Morris
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Salem
authors.affiliation: Northwestern University, Chicago, IL, USA.
authors.forename: Halla
authors.initials: H
authors.lastname: Nimeiri
authors.affiliation: University of Southern California, Los Angeles, CA, USA.
authors.forename: Syma
authors.initials: S
authors.lastname: Iqbal
authors.affiliation: Washington University, St Louis, MO, USA.
authors.forename: Preet
authors.initials: P
authors.lastname: Singh
authors.affiliation: The Ohio State University, Columbus, OH, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Ciombor
authors.affiliation: University of Chicago, Chicago, IL, USA.
authors.forename: Blase
authors.initials: B
authors.lastname: Polite
authors.affiliation: University of Wisconsin, Madison, WI, USA.
authors.forename: Dustin
authors.initials: D
authors.lastname: Deming
authors.affiliation: Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Chan
authors.affiliation: Decatur Memorial Hospital, Decatur, IL, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Wade
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.affiliation: The Ohio State University, Columbus, OH, USA.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Vence
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Blando
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Armeen
authors.initials: A
authors.lastname: Mahvash
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Wai Chin
authors.initials: WC
authors.lastname: Foo
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Chimela
authors.initials: C
authors.lastname: Ohaji
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Manolo
authors.initials: M
authors.lastname: Pasia
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gail
authors.initials: G
authors.lastname: Bland
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Aki
authors.initials: A
authors.lastname: Ohinata
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Rogers
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Mehdizadeh
authors.affiliation: Guardant Health, Redwood City, CA, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Banks
authors.affiliation: Guardant Health, Redwood City, CA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Lanman
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: National Cancer Institute, Bethesda, MD, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Streicher
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: James
authors.initials: J
authors.lastname: Allison
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Padmanee
authors.initials: P
authors.lastname: Sharma
authors.affiliation: The University of Texas-MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ceng@mdanderson.org.
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D016022:Case-Control Studies; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D000077594:Nivolumab; D011379:Prognosis; D011446:Prospective Studies; D066066:Response Evaluation Criteria in Solid Tumors; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077594:Nivolumab