First-line treatment with Keytruda (pembrolizumab) — alone or in combination with standard chemotherapy — significantly prolongs survival of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), compared to standard treatment, according to interim results of a Phase 3 clinical trial.
The results, “KEYNOTE-048: Phase III study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC),” were in with a scientific poster at the European Society for Medical Oncology (ESMO) 2018 Congress, Oct. 19-23, in Munich, Germany.
Keytruda, developed by Merck (known as MSD outside the U.S. and Canada), is an immunotherapy that blocks a mechanism frequently used by cancer cells to evade anti-tumor immune responses. This mechanism involves the interaction between the PD-1 receptor in cells of the immune system and its ligand PD-L1 in cancer cells.
The current first-line standard of care treatment for this type of aggressive cancer, known as EXTREME regimen, consists of platinum-based chemotherapy — Platinol (cisplatin) or Paraplatin (carboplatin) — and Adrucil (5-fluorouracil) chemotherapy, in combination with Erbitux (cetuximab). About 35% of patients respond to treatment, resulting in a median survival of a little more than 10 months.
The randomized, open-label, Phase 3 trial (NCT02358031), also known as KEYNOTE-048, is evaluating Keytruda — alone or in combination with standard chemotherapy (platinum-based and Adrucil chemotherapy) — as a first-line treatment in patients with head and neck squamous cancer that has relapsed or spread to other parts of the body.
The trial’s primary goals are overall survival and progression-free survival (PFS), or the time a patient lives without cancer progression, in patients whose tumors produce PD-L1 and in all patients regardless of PD-L1 presence.
PD-L1 presence was measured by a combined positive score (CPS), which includes levels of PD-L1 on both the tumor and surrounding cells. Patients with positive detection of PD-L1 were divided into two CPS categories: equal or above 20 (high levels), and equal or above one (low levels).
The trial’s secondary goals include treatment response rate and global health status or quality of life.
KEYNOTE-048 enrolled 882 patients with head and neck squamous cancer who had not received prior systemic therapy for relapsed or metastatic disease. Patients were randomized to receive either Keytruda alone (300 patients), Keytruda in combination with standard chemotherapy (281 patients), or standard therapy (300 patients), for up to two years.
Barbara Burtness, the study’s first-author and co-director of the Development Therapeutics Research Program, at Yale Cancer Center, presented the KEYNOTE-048 results collected until June 13, 2018, with a minimum follow-up of about 17 months.
Keytruda alone significantly prolonged the survival of patients with high (14.9 months) or low (12.3 months) levels of PD-L1, compared to standard treatment (10.3 and 10.7 months, respectively).
While fewer patients responded to Keytruda (17%) than to standard therapy (36%), the median duration of treatment response was longer in the Keytruda group (20.9 months), compared to that of the standard treatment group (4.5 months).
The combination of Keytruda and standard chemotherapy also significantly extended the patients’ survival (13.0 months), compared to standard care (10.7 months). Among patients producing high or low levels of PD-L1, no differences in overall survival were found between both treatment groups.
Treatment response rates were similar between patients receiving the combo therapy (35.6%) and those receiving standard care (36.3%), but the response duration also was prolonged in the combo therapy group.
The results also showed that Keytruda alone or combined with standard chemotherapy did not prolong patients’ PFS, compared with standard treatment.
The safety profiles of the three treatment regimens were consistent with those reported in previous clinical studies. Keytruda alone was less toxic than standard treatment, while Keytruda combined with chemotherapy showed similar toxicity to standard treatment.
The researchers noted that these interim data support Keytruda alone or in combination with standard chemotherapy as new-first line treatments for recurrent or metastatic head and neck squamous cancer.
“Pembrolizumab [Keytruda] appears to prolong life even when the cancer continues to grow,” Burtness said in a press release.
“Whether pembrolizumab is given alone or with chemotherapy may depend on PD-L1 expression and we are conducting analyses to answer this question,” she added.
Tanguy Seiwert, MD, director of the Head and Neck Cancer Programme at the University of Chicago Medicine said that “separate analyses are needed in patients who have tumors with low or absent PD-L1 expression, where there is potentially less benefit,” and that “the usefulness of other biomarkers to select patients for treatment, such as tumor mutational burden, should also be examined.”