Nick Mulcahy

May 29, 2015

CHICAGO — In another noteworthy outcome for a PD-1 immunotherapy; nearly one-quarter of patients with advanced head and neck cancer responded to treatment with pembrolizumab (Keytruda, Merck), according to the KEYNOTE 012 trial.

The efficacy is "remarkable," said lead investigator Tanguy Seiwert, MD, from the University of Chicago, during a press briefing here at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting.

Specifically, 29 of 117 (24.8%) patients in the expansion cohort of a phase 1 trial met the RECIST criteria for response; there were 28 partial responses and one complete response.

Notably, 25 of these responders continue to do so and, thus, are still on treatment and have a "durable" response; the average follow-up time is 5.7 months.

The overall response rate is double that of cetuximab (Erbitux, Bristol Myers-Squibb/Eli Lilly), which is the only targeted therapy for these patients, said Dr Seiwert.

"We have high hopes that immunotherapy will change the way we treat head and neck cancer," he noted in a press statement.

"This is yet another exciting example where PD-1 immunotherapy might work better and more reliably than existing drugs," said Gregory A. Masters, MD, a medical oncologist at Christiana Care's Helen F. Graham Cancer Center in Newark, Delaware, and an ASCO expert.

In the current study, the overall response rate is "on par" with that seen with immunotherapy in lung cancer, said Stephen Liu, MD, a medical oncologist at Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, who was not involved with the study.

"There are patients surviving 1 year and longer," he explained.

Dr Liu believes such benefits could occur in the head and neck setting. "That's why this is promising," he said. "We have a chance for durable responses that are meaningful in head and neck cancer too."

"It's a fun time," Dr Liu declared in interview with Medscape Medical News.

But the current treatment landscape is not inspiring, he noted. "While there are options, there are no good options," he said.

While there are options, there are no good options.

Currently, standard initial treatment involves platinum-based doublet chemotherapy with or without cetuximab. Second-line options include methotrexate, docetaxel, and cetuximab. Only 10% to 13% of patients respond to single-agent cetuximab.

Pembrolizumab is also effective in human papillomavirus (HPV)-negative and HPV-positive patients, said Dr Liu.

In their study, Dr Seiwert and colleagues found overall response rates with pembrolizumab of 27.2% in the 81 HPV-negative patients and 20.6% in the 34 HPV-positive patients.

This is notable because there appears to be less efficacy with EGFR inhibitors, such as cetuximab, in HPV-positive head and neck cancers, Dr Seiwert reported.

All the study patients had recurrent or metastatic squamous cell carcinoma of the head and neck and received a fixed dose of pembrolizumab 200 mg, administered as an infusion every 3 weeks. Average age was 58.9 years, and 83.3% of the patients were male.

Most of the study cohort was mostly heavily pretreated, and 59% had received at least two previous therapies.

Twenty-nine (24.8%) of the study participants had stable disease, said Dr Seiwert. Thus, when added to the overall response rate, there was a disease control rate of just about 50%.

Importantly, patients were not selected for the study on the basis of PD-L1 status. This biomarker predicts response to PD-1/PD-L1 immunotherapies such as pembrolizumab.

"The diversity of patients who responded is greater than in any previous clinical trial," Dr Masters said about the patient mix.

New treatments for advanced head and neck cancer are very much needed, said Dr Seiwert.

Recurrent/metastatic disease carries a poor prognosis; median overall survival is approximately 13 months.

Currently, standard initial treatment involves platinum-based doublet chemotherapy with or without cetuximab, according to ASCO press materials. Second-line options include methotrexate, docetaxel, and cetuximab. Only 10% to 13% of patients respond to single-agent cetuximab.

The most common adverse events of any grade were fatigue (15.2%), hypothyroidism (9.1%), and rash (7.6%). Adverse events of grade 3 or higher only occurred in 9.8% of patients. Two patients developed treatment-related pneumonitis of grade 3 or higher, and one developed treatment-related colitis of grade 3 or higher.

The adverse-event profile is better than that of current standard treatment, observed Dr Masters.

But more study is needed, he added. "We still need larger studies and longer follow-up to assess the impact of this treatment on patient survival."

Dr Seiwert also said that there might be a biomarker that helps predict which head and neck cancer patients will respond to immunotherapy. An interferon-gamma expression signature has shown promise and will be reported during the meeting (abstract 6017).

Currently, there are two ongoing phase 3 studies comparing pembrolizumab with standard treatment in patients with advanced head and neck cancer, according to meeting press materials.

The study was funded by Merck. Dr Seiwert reported financial relationships with pharmaceutical companies, including Merck. Some of the study authors are employees of Merck. Dr Masters has disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2015 Annual Meeting: Abstract LBA6008. To be presented June 1, 2015


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