ASCO 2016-IMMUNOTHERAPY FOR ANAL CANCER

The immune checkpoint blockade nivolumab (Opdivo, Bristol-Myers Squibb Company) has shown promising results for patients with squamous cell carcinoma of the anal canal (SCCA).

The findings, which were presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting, showed a 24% response rate to nivolumab, including two complete responses.

"Anal cancer refractory to chemotherapy and radiation can respond to PD-1 inhibitory agents — good news to bring home to our clinics," commented Richard Goldberg, MD, physician-in-chief, Ohio State University Comprehensive Cancer Center—James Cancer Hospital and Solove Research Institute, Columbus.

Speaking at a Highlights of the Day session for gastrointestinal (colorectal) cancer, Dr Goldberg noted that although this was a small study, it was "really the first prospective phase 2 trial completed in refractory metastatic SCCA in the United States.

"It showed that single-agent nivolumab was well tolerated and fulfilled the primary endpoint of response," he said. "And it opens the door to the use of immunotherapy in another one of the virally associated cancer, this one with human papilloma virus [HPV]."

He emphasized that these findings may offer a new, badly needed treatment option to this population.

"This abstract provides us with something beyond the NCCN guidelines on metastatic anal cancer, which tell us that 5-FU/cisplatin is recommended for metastatic disease," Dr Goldberg said. "There is basically one validated option for these patients, and at least in my clinic, these patients run out of options long before they run out of the desire for more options."

Although SCCA is a relatively rare disease, its incidence has been increasing by 2% to 3% per year. It is estimated that more than 8000 cases will be diagnosed in the United States this year.

"About 20% of patients present with metastatic SCCA, and there is currently no standard of care for patients with metastatic refractory disease," explained study author Cathy Eng, MD, professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center in Houston, who presented the findings at the meetinG.

SCCA is primarily driven by HPV, which accounts for approximately 80% to 95% of cases. "The role of HPV in the tumorigenesis of this disease provides rationale for the use of immune checkpoint agents as a novel treatment in a virally driven disease," she said.

"This is the first study to investigate the use of immunotherapy in this patient population," said Dr Eng.

Study Details

The study was conducted through the National Cancer Institute's (NCI's) Experimental Therapeutics Clinical Trials Network (ETCTN), which was created by the NCI to evaluate therapies using a coordinated, collaborative, and inclusive team-based approach to early-phase experimental therapeutic clinical trials.

A total of 39 patients were screened across the ETCTN within a 5-month period; 37 patients were enrolled in the trial and received treatment, and 34 were evaluable for response.

All patients received nivolumab (3 mg/kg) IV every 2 weeks. Optional pretreatment and on-treatment tissue biopsies were performed, and plasma samples were collected for immune biomarkers and HPV/p16 status. Two patients were HIV-positive.

The median number of prior therapies was two (range, one to eight). PD-L1 expression was not required for participation in the study.

Of the 34 patients who were eligible for evaluation, two patients (5.4%) achieved a complete response, seven (18.9%) had a partial response, 17 (45.9%) had stable disease, and eight (21.6%) had progressive disease.

The overall response rate in the intent-to-treat group was 24.3% (n = 9). In the evaluable group, the overall response rate was 26.5% (n = 9).

Progression-free survival was 3.9 months, which Dr Eng explained was "not surprising, given that our data have shown a progression-free survival of about 5 months in treatment-naive patients with cytotoxic chemotherapy."

Dr Eng pointed out a few individual cases. One patient with dermal and liver metastases and lymph node involvement had undergone two previous lines of therapy. "She just came off treatment after 23 doses and has been on study for 11 months," she said. "Her dermal metastases completely resolved with treatment."

At baseline, CD8, PD1, and PDLI expression was increased in responders as compared with nonresponders, she added.

There were very few grade 3 toxicities, which included fatigue, anemia, rash, and hyperthyroidism. There was one incidence of pneumonitis.

The study was funded by MD Anderson's HPV Moon Shots Program, the HPV Anal Cancer Foundation, the E. B. Anal Cancer Fund, and a philanthropic donation. Dr Eng and several coauthors report relationships with industry, as noted in the abstract. Dr Goldberg has relationships with Baxter, Biothera, Forty Seven, Immunocare Therapies, Immunovative Therapies, Kanghong Pharma, Lilly, Merck, Momenta Pharmaceuticals, Novo Nordisk, Pfizer, Sirtex Medical, Taiho Pharmaceutical, Targovax, Bayer (Inst), Bristol-Myers Squibb (Inst), Immunomedics (Inst), Sanofi (Inst), Amgen, and Merck KGaA.

American Society of Clinical Oncology (ASCO) 2016 Annual Meeting: Abstract 3503. Presented June 6, 2016.