TY - JOUR
T1 - Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673)
T2 - a multicentre, single-arm, phase 2 study
AU - Morris, Van K.
AU - Salem, Mohamed E.
AU - Nimeiri, Halla
AU - Iqbal, Syma
AU - Singh, Preet
AU - Ciombor, Kristen
AU - Polite, Blase
AU - Deming, Dustin
AU - Chan, Emily
AU - Wade, James L.
AU - Xiao, Lianchun
AU - Bekaii-Saab, Tanios
AU - Vence, Luis
AU - Blando, Jorge
AU - Mahvash, Armeen
AU - Foo, Wai Chin
AU - Ohaji, Chimela
AU - Pasia, Manolo
AU - Bland, Gail
AU - Ohinata, Aki
AU - Rogers, Jane
AU - Mehdizadeh, Amir
AU - Banks, Kimberly
AU - Lanman, Richard
AU - Wolff, Robert A.
AU - Streicher, Howard
AU - Allison, James
AU - Sharma, Padmanee
AU - Eng, Cathy
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background 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. Methods 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. Results 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. Interpretation 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. Funding 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.
AB - Background 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. Methods 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. Results 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. Interpretation 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. Funding 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.
UR - http://www.scopus.com/inward/record.url?scp=85013224907&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(17)30104-3
DO - 10.1016/S1470-2045(17)30104-3
M3 - Article
C2 - 28223062
AN - SCOPUS:85013224907
SN - 1470-2045
VL - 18
SP - 446
EP - 453
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 4
ER -