Pembrolizumab demonstrates significant clinical activity in heavily pretreated HNSCC

CHICAGO — Pembrolizumab conferred clinically significant antitumor activity in patients with recurrent or metastatic head and neck squamous cell carcinoma who were previously treated with platinum and cetuximab therapies, according to preliminary results from the phase 2, single-arm, KEYNOTE-055 study presented at the ASCO Annual Meeting.

Pembrolizumab (Keytruda, Merck) also appeared well tolerated in this population.

“There really are no effective treatments for recurrent or metastatic head and neck cancer that is refractory to both platinum chemotherapy and cetuximab,” Joshua M. Bauml, MD, assistant professor of medicine at the Perelman School of Medicine at the University of Pennsylvania, said during a presentation. “The most commonly used reference population is patients treated with methotrexate. However, the overall response rate to methotrexate is only about 5%.”

Pembrolizumab previously showed promising antitumor activity in recurrent or metastatic HNSCC in the KEYNOTE-012 trial.

For this reason, Bauml and colleagues sought to assess the efficacy of pembrolizumab in 172 patients with recurrent or metastatic HNSCC who experienced progression on platinum and cetuximab therapies.

The analysis includes data from the first 50 patients enrolled (median age, 59; 80% male; 84% received two or more prior lines of therapy for metastatic disease). Additional updated data included all-dosed patients with at least 6 months of follow-up (n = 92).

Patients had measurable disease and ECOG performance scores of 0 to 1. PD-L1 expression was not required for enrollment in the study; however, researchers obtained biopsies to determine any relationship between PD-L1 and benefit.

Patients received 200 mg pembrolizumab every 3 weeks, for 2 years or until progression of disease.

ORR served as the primary outcome.

Median follow-up was 6.8 months.

Median PFS was 2.1 months and median OS was 6 months. Twenty-four percent of patients achieved 6-month PFS and 65% achieved 6-month OS.

In the first 50 dosed patients, the ORR was 18%, which included only partial responders. An additional 18% of patients had stable disease (95% CI, 8.6-31.4).

Among those with at least 6 months of follow-up data, the ORR was 17% and included only partial responders; an additional 19% of patients achieved stable disease.

When patients were separated by HPV status, researchers observed a small improvement in the ORR for HPV–positive vs. HPV–negative patients. However, the data are too preliminary to make any conclusive statements regarding the role of pembrolizumab according to HPV status, Bauml said.

Patients with PD-L1–positive disease also demonstrated a higher ORR (17% vs. 8%).

“However, when looking at the rate of PD-L1-positivity, it is very high, at 76 of the 92 patients,” Bauml said.

Fifty-four percent of patients experienced a decrease in target lesions.

At the time of data cutoff, median time to response was 2 months and 75% of patients remained in response.

The most common adverse event was fatigue (15%). Grade 3 to 5 toxicities occurred in 12% of patients, which included one treatment-related death.

Three patients discontinued treatment due to treatment-related adverse events.

“This is the first report of phase 2 data showing efficacy of pembrolizumab in recurrent and metastatic HNSCC,” Bauml said. “This was a heavily pretreated population, of which 84% had at least two lines of systemic therapy prior to enrollment.

“Survival data were encouraging at 8 months, compared to that of our historical reference population with survival of only about 6 months,” Bauml added. “It is very fair to say that pembrolizumab is a promising therapy for this patient population with very limited options.”

The phase 3 KEYNOTE-040 and KEYNOTE-048 studies also are investigating the clinical benefit of pembrolizumab compared with and in addition to traditional cytotoxic chemotherapy. – by Jennifer Southall

Reference :

Bauml J, et al. Abstract 6011. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosure : Bauml reports research funding and consultant roles with AstraZeneca, Bristol-Myers Squibb, Carevive Systems, Clovis Oncology and Merck. Please see the abstract for a list of all other researchers’ relevant financial disclosures.