Studies show early success for pre-surgical immunotherapy in liver cancer, cutaneous head and neck cancer

Early results from two MD Anderson studies show promising responses to neoadjuvant (pre-surgical) checkpoint inhibitors in patients with advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), a type of skin cancer, and hepatocellular carcinoma (HCC), a type of liver cancer. Neither disease currently has an effective FDA-approved chemotherapy or can be cured through surgery alone. Initial results from both studies were shared as late-breaking abstracts at the European Society for Medical Oncology Congress 2019 today in Barcelona.

ABSTRACT LBA47: Randomized, open-label, perioperative phase II study evaluating nivolumab alone versus nivolumab plus ipilimumab in patients with resectable hepatocellular carcinoma (HCC)

This study is the first to evaluate neoadjuvant immunotherapy for hepatocellular carcinoma treatment, which has a high recurrence rate following surgery. In the phase II clinical trial, patients were randomized to receive three cycles of nivolumab alone or nivolumab and ipilimumab prior to surgery. Both arms continued to receive adjuvant immunotherapy for up to two years after surgery. Pathological complete response was observed in 25% of patients (five of the 20 patients at the time of interim analysis; two from the nivolumab arm and three from the combination arm).

“Up to 50% of patients who undergo surgery for HCC have their tumors recur within two years,” said lead author Ahmed Kaseb, M.D., professor of Gastrointestinal Medical Oncology. “The promise of this study is a chance to lower recurrence and improve survival for this patient population.”

The study’s primary objective is safety/tolerability. Five patients in the combination arm and one in the nivolumab arm experienced grade 3 or 4 toxicity prior to surgery, but surgical resection was not delayed. The trial is still actively recruiting and a multicenter version of the trial is in development. See the abstract and co-authors here.

ABSTRACT LBA74: Phase II study of neoadjuvant cemiplimab prior to surgery in patients with stage III/IV (M0) cutaneous squamous cell carcinoma of the head and neck (CSCC-HN)

The FDA approved the PD-1 inhibitor cemiplimab for non-resectable, metastatic cutaneous squamous cell carcinoma in 2018. In the phase II clinical trial presented at ESMO, patients with advanced squamous cell carcinoma of the head and neck who were candidates for surgery and radiation received two doses of cemiplimab every three weeks prior to surgery. A pathologic complete response (no residual cancer) or major pathologic response (≤10% residual cancer) was observed in 70% of patients enrolled (14 of 20 total patients). As a result, most patients were able to forego planned post-surgical radiation therapy.

“The traditional combination of surgery and radiation therapy can be disfiguring for patients with this disease. This study represents an opportunity to transform how we treat advanced squamous cell carcinoma,” said lead author Neil Gross, M.D., professor of Head and Neck Surgery. “It’s a small study, but a larger, multinational phase II trial is already planned to confirm the results.”  

The study’s primary endpoint, overall response rate was 30%. There were no grade ≥3 adverse events, no surgical delays and no loss of opportunity for curative surgery after treatment.  Correlative analyses are in progress. See the abstract and co-authors here.