Nivolumab Active With Few Toxicities In Advanced Anal Cancer

The PD-1 inhibitor nivolumab showed single-agent activity in previously treated patients with squamous cell carcinoma of the anal canal, resulting in an overall response rate of 24.3%.

Cathy Eng, MD

Cathy Eng, MD

The PD-1 inhibitor nivolumab (Opdivo) showed single-agent activity in previously treated patients with squamous cell carcinoma of the anal canal (SCCA), resulting in an overall response rate (ORR) of 24.3%, according to findings from a single-arm phase II trial published inThe Lancet Oncology.1

At a median follow-up of 10.1 months (95% CI, 9.4-12.2), 2 patients had a complete response and seven others had partial responses. Seventeen patients had stable disease and 8 patients experienced progressive disease. Three patients were not evaluable for response. The median overall survival (OS) was 11.5 months (95% CI, 7.1 to not estimable) and the estimated 1-year OS rate was 48% (95% CI, 32-74).

“These are previously-treated patients and there’s no established standard of care, so to have a single agent have activity with very few toxicities is quite exciting for this patient population,” co-author Cathy Eng, MD, professor of gastrointestinal medical oncology at MD Anderson Cancer Center, said in an interview withTargeted Oncology. “This patient population doesn’t get a lot of recognition. Rare cancers are often overlooked, not just this one.”

Eng said 10% to 20% of patients present with advanced SCAA and a similar number will progress to metastatic disease. Moreover, incidence is increasing by as much as 2% annually in Western countries.2“ThatThe Lancet Oncologywas willing to publish a small phase II trial in a rare cancer is recognition of the fact that there is an unmet need to find treatment options for these patients,” she added.

The phase II study (NCI9673) was conducted at 10 US academic centers. Eligible patients were immunotherapy-naïve, but had received prior treatment.

Four of the first 12 participants had partial response in the first stage of the of the study. That allowed researchers to recruit 25 additional patients for the second stage. Patients were assigned to 3 mg/kg IV of nivolumab every 2 weeks, and received a median of 6 doses. A total of 37 patients received at least one dose of nivolumab and were included in these findings.

median progression-free survival (PFS) was 4.1 months (95% CI, 3.0-7.9), up slightly from the 3.9 months reported initially. The 6-month PFS rate was 38% (95% CI, 24-60). Researchers noted that the longest duration of treatment was almost 1 year and was continuing as of the data cutoff date of May 2016.

Seven (78%) of the 9 responding patients had durable responses, with a median duration of 5.8 months (IQR, 3.9—8.1). As of the data cutoff, six responding patients remained on study. The longest ongoing duration of response of 10.4 months. Two patients were HIV-positive, one of whom had partial radiographic response. Among the responders, the median reduction from baseline in target lesions was 70% (IQR, 57-90).

By immunohistochemistry, responders had higher baseline percentages of T cells expressing CD8 and granzyme B than did nonresponders. Responding patients also had higher concentrations of PD-1 in immune cells in the tumor microenvironment compared with nonresponders. Furthermore, responders were more likely to express PD-1 in tumor cells.

Researchers observed grade 3 toxicities in 5 patients; 2 patients experienced anemia, and 1 patient each had grade 3 fatigue, rash, and hyperthyroidism. Researchers recorded a single incidence of grade 2 pneumonitis, and there were no unexpected serious adverse events in patients with HIV. There were no treatment-related deaths recorded in the study, but 43% of patients died due to progression.

Eng said this study is being amended to become a larger randomized study. Researchers hope to begin enrollment within 3 months.

Writing in an accompanying editorial, Stefano Cascinu, MD, PhD, with the Università di Modena e Reggio Emilia in Modena, Italy, praised the researchers for their results and said the study raises as many good questions as it answers.3

“Much is unknown about using immunotherapy for the treatment of SCCA: how can we select patients who will benefit? How can other patients be made sensitive to these drugs? And what role might nivolumab have in the treatment of locoregional disease together [with] chemoradiotherapy?” he wrote. “Even so, Morris and colleagues have shown that nivolumab seems to benefit a quarter of patients. For the first time in 20 years, there is something new in the treatment of SCCA.”


  1. Morris VK, Salem ME, Nimeiri H, et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.Lancet Oncol.2017;18:446-453.
  2. van der Zee RP, Richel O, de Vries HJC, Prins JM. The increasing incidence of anal cancer: can it be explained by trends in risk groups?Neth J Med.2013;71:401-411.
  3. Cascinu S. Anal cancer: from an orphan disease to a curable malignancy?Lancet Oncol.doi:
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