Opdivo for anal cancer – pro
Previously treated patients with squamous cell carcinoma of the anal canal (SCCA) saw a 24.3 percent overall response rate (ORR) when treated with Opdivo (nivolumab), a PD-1 inhibitor, according to findings from a single-arm phase 2 trial published in The Lancet Oncology. IT was smalls study. 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 Opdivo every two weeks, and received a median of six doses. A total of 37 patients received at least one dose of Opdivo and were included in these findings.
The median progression-free survival (PFS) was 4.1 months, up slightly from the 3.9 months reported initially. The six-month PFS rate was 38 percent. Researchers noted that the longest duration of treatment was almost one year and was continuing as of the data cutoff date of May 2016.
Seven (78 percent) of the nine responding patients had durable responses, with a median duration of 5.8 months. 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 percent.
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 five patients; two patients experienced anemia, and one 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 percent of patients died due to progression.
Morris VK et al, Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.Lancet Oncol. 2017 Apr;18(4):446-453.