In a phase II trial reported in The Lancet Oncology, Morris et al found that nivolumab (Opdivo) was active in previously treated unresectable metastatic squamous cell carcinoma of the anal canal. This malignancy is associated with human papillomavirus (HPV) infection, with the rationale for anti–programmed cell death protein 1 (PD-1) treatment being that intratumoral HPV oncoproteins act to upregulate immune checkpoint proteins.
In the trial, 37 patients with refractory disease from 10 U.S. centers were treated with nivolumab at 3 mg/kg every 2 weeks. The primary endpoint was response on Response Evaluation Criteria in Solid Tumors (RECIST v1.1) in the intent-to-treat population.
Patients had a median age of 56 years, 90% were white, and 73% were female. A total of 41% had local recurrence, and all had distant metastases. Patients had received a median of two prior lines of therapy (range = 1–7).
At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The median follow-up time for all patients was 10.1 months.
Among the 37 patients, 9 patients (24%, 95% confidence interval [CI] = 15%–33%) had responses, including a complete response in 2. Durable responses were seen in 7 patients, with a median duration of response of 5.8 months among all patients. At data cutoff, 6 responders remained on study, with the longest ongoing response being 10.4 months. Stable disease was observed in 17 patients (47%), yielding a disease control rate of 72%. Median reduction in target lesions in responders was 70%.
Median progression-free survival was 4.1 months, and 6-month progression-free survival was 38%. Median overall survival was 11.5 months, and estimated 1-year overall survival was 48%.
The most common adverse events of any grade were anemia (70%), fatigue (68%), and rash (30%); grade 3 adverse events consisted of anemia in two patients, fatigue in one patient, rash in one patient, and hypothyroidism in one patient. One patient developed treatment-related grade 2 pneumonitis, which required steroid therapy and treatment interruption. Another patient required immunosuppressant treatment for treatment-related hypothyroidism. No serious adverse events were reported.
The investigators concluded: “To our knowledge, this is the first completed phase 2 trial of immunotherapy for [squamous cell carcinoma of the anal canal]. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic [squamous cell carcinoma of the anal canal]. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease.”
The study was funded by the National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.
Cathy Eng, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of The Lancet Oncology article.
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