Top Takeaways from ASCO: Advanced squamous cell carcinoma of the head and neck

Data from two high-profile trials presented at the ASCO Annual Meeting assessed treatment options and quality of life for patients with advanced head and neck squamous cell carcinoma.

Two HemOnc Today Editorial Board members discussed the take-home messages and long-term implications of these findings.

KEYNOTE-012

Results from the expansion cohort of the KEYNOTE-012 trial showed pembrolizumab (Keytruda, Merck), an anti–PD-1 antibody, demonstrated strong activity in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Tanguy Seiwert, MD, assistant professor of medicine and associate head and neck cancer program leader at University of Chicago, and colleagues evaluated 132 patients (mean age, 58.9 years; 83% male). More than half (59%) of patients underwent at least two previous lines of therapy for recurrent disease.

All patients received pembrolizumab 200 mg via IV every 3 weeks. Treatment continued until disease progression.

Overall response rate served as the primary endpoint. Secondary endpoints included PFS and OS.

Seiwert reported results for 117 patients (HPV-positive, n = 34; HPV-negative, n = 81). Median follow-up was 5.7 months (range, 0.2-8.7).

Results showed 56% of patients experienced some decrease in tumor size. Overall, 29 patients (24.8%) demonstrated objective response and 29 (24.8%) demonstrated stable disease, equating to a disease control rate of about 50%. Median time to response was 9 weeks (range, 7.6-18).

Researchers reported comparable response rates among patients with HPV-negative tumors (27.2%) and HPV-positive tumors (20.6%).

“The results are quite striking,” Barbara Ann Burtness, MD, professor of medicine (medical oncology), clinical research program leader of the head and neck cancers program and co-director of the developmental therapeutics research program at Yale University, told HemOnc Today. “The agent showed continued activity. Some of the responses were quite durable and there’s quite an interesting-looking tail on the curve.”

Barbara Ann Burtness

Trials of pembrolizumab against standard-of-care treatment for head and neck cancers are beginning throughout the world, Burtness said.

“We’re also likely to see research coming forward that helps us understand why those patients who are not responsive to the agent are resistant in such a way that we might, next year, be talking about novel immunotherapy combinations for head and neck cancer,” she said.

Panitumumab plus radiation

Panitumumab (Vectibix, Amgen) in combination with radiation did not prove superior to the combination of radiation and standard chemotherapy in patients with locoregionally advanced HNSCC, according to results of a phase 3 trial.

Lillian Siu MD, FRCPC, senior medical oncologist and clinical leader of the tumor immunotherapy program at Princess Margaret Hospital in Toronto, and colleagues from the National Cancer Institute of Canada clinical trials group assessed treatment outcomes and quality of life in 320 patients.

Researchers randomly assigned patients 1:1 to standard fractionation radiotherapy (70 Gy in 35 doses over 7 weeks) and cisplatin 100 mg/m2 via IV every 3 weeks vs. accelerated fractionation radiotherapy (70 Gy in 35 doses over 6 weeks) and panitumumab 9 mg/kg via IV.

Median follow-up was 46.4 months.

“The primary endpoint was [PFS],” David J. Adelstein, MD, staff physician in the department of hematology and medical oncology at Cleveland Clinic’s Taussig Cancer Institute and professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, told HemOnc Today. “That was not different between the two treatment arms. The secondary endpoints — including [OS], local control, regional control and distant control — were also the same between the two treatment arms. [The researchers] couldn’t identify any subgroup that benefitted from one treatment or the other.”

David J. Adelstein

Researchers reported 2-year PFS of 76% among patients assigned panitumumab and accelerated fractionation radiotherapy vs. 73% among patients assigned standard fractionation radiotherapy and cisplatin (HR = 0.95; 95% CI, 0.6-1.5). Two-year OS also was similar between groups (88% vs. 85%; HR = 0.89; 95% CI, 0.54-1.48).

In addition, results showed no difference in quality of life between treatment groups.

“They measured this in a number ways. They looked at feeding tube use and they looked at a number of quality-of-life instruments, and there wasn’t any meaningful difference between the two treatments,” Adelstein said. “Panitumumab was not demonstrated to be superior or inferior to cisplatin. The overall toxicity burden was about the same and the quality of life was about the same.”

As a result, panitumumab may not be the best choice for patients with locoregionally advanced HNSCC, Adelstein said.

“The take-home message is pretty straightforward,” he said. “If you look at the drug acquisition cost of these agents — the cost of three doses of cisplatin vs. three doses of panitumumab, the doses that were used in the study — in an average-sized individual, the cost of cisplatin is approximately $100 and the cost of panitumumab is greater than $20,000. So, in this era of value-based care, there was no improvement in outcome and there was this huge difference in cost.

“It really tells us that panitumumab should not replace cisplatin as the preferred treatment in this setting which, I think, is an important message,” Adelstein said. “The recently completed — and considerably larger — RTOG 1016 trial, which compared radiation and cisplatin with radiation and the EGFR inhibitor cetuximab (Erbitux; Bristol-Myers Squibb, Lilly) in an exclusively p16-positive patient population with oropharynx cancer will help further define the role of these agents in current management.” – by Julia Ernst

References:

The following all were presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Ringash J, et al. Abstract 6053.

Seiwert TY, et al. Abstract LBA6008.

Siu LL, et al. Abstract 6000.

Disclosure: Burtness reports research funding from and a consultant role with Merck. Adelstein reports no relevant financial disclosures.