In the phase III comparative CheckMate 141 trial, nivolumab demonstrated a “significant improval in survival” in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), compared with therapy of the investigator’s choice, according to Robert L. Ferris, MD, PhD, FACS, of the University of Pittsburgh Cancer Institute (Abstract 6009). There were fewer treatment-related adverse events with the PD-1 inhibitor than with investigator’s choice therapy, Dr. Ferris said, and nivolumab stabilized patient-reported quality-of-life outcome measures, whereas the investigator’s choice therapy led to meaningful declines in function and worsening of symptoms.
Dr. Robert L. Ferris
“Nivolumab is a new standard-of-care option for patients with refractory or metastatic HNSCC after platinum-based therapy,” Dr. Ferris said.
Dr. Ferris presented the trial results at the “Harnessing the Immune System in Head and Neck Cancer: Evolving Standards in Metastatic Disease” Clinical Science Symposium on June 6. He noted that in this trial of patients whose disease had progressed after platinum-based therapy, nivolumab doubled the 1-year overall survival (OS) rate, with 36.0% OS for the immunotherapeutic drug compared with 16.6% for the investigator’s choice therapy. These top-line results were presented at the 2016 American Association of Cancer Research meeting1; Dr. Ferris presented data the additional endpoints of quality of life, correlative biomarkers, and safety.
There is an extremely poor prognosis for patients with platinum-refractory recurrent or metastatic HNSCC, with median OS of 6 months or fewer. Previous research, by Dr. Ferris and others, has shown that HNSCC can express T-cell suppressive ligands, such as PD-L1, thereby evading host immune response. PD-L1 is frequently expressed on HNSCC cells, both HPV-positive and -negative.
The phase III CheckMate 141 study enrolled patients with HNSCC aged 18 and older with ECOG status 0 or 1, and with disease progression within 6 months after the most recent dose of platinum-based therapy. Patients were enrolled regardless of PD-L1 status and irrespective of number of previous lines of therapy. Immunohistochemistry testing for p16 was performed to determine HPV status. Patients were randomly assigned 2:1 to nivolumab (3 mg/kg intravenous [IV] every 2 weeks) or investigator’s choice of single-agent therapy with methotrexate (40 mg/m² IV weekly), docetaxel (30 mg/m² IV weekly), or cetuximab (400 mg/m² IV once, then 250 mg/m² weekly).
OS was compared between arms and by PD-L1 expression and HPV (p16) status. Nivolumab demonstrated a survival benefit in the overall study population, regardless of PD-L1 expression or p16 status, Dr. Ferris said. The magnitude of the OS benefit of nivolumab was greater in patients expressing PD-L1 at 1% or more (HR 0.55, 95% CI [0.36, 0.83]) compared with those expressing PD-L1 at less than 1% (HR 0.89, 95% CI [0.54, 1.45]). However, increasing levels of PD-L1 expression ( ≥ 5%, ≥ 10%) did not result in further OS benefit.
The OS benefit was greater with nivolumab than investigator’s choice therapy in both patients who were p16 positive (HR 0.56, 95% CI [0.32, 0.99]) and p16 negative (HR 0.73, 95% CI [0.42, 1.25]). When OS was analyzed for both PD-L1 expression and p16 status, the hazard ratios favored nivolumab for all subgroups.
Treatment-related adverse events of any grade were lower in the nivolumab arm (58.9%) than the investigator’s choice therapy arm (77.5%). Serious (grade 3 or 4) treatment-related adverse events were also lower in the nivolumab arm (13.1%) than in the investigator’s choice therapy arm (35.1%). Patient-reported outcome measures for quality of life were assessed based on two EORTC scales. Treatment with nivolumab stabilized the outcome measures of physical function, social function, absence of sensory problems, and absence of trouble with social contact, whereas the investigator’s choice therapy led to meaningful declines in function and worsening of symptoms.
Dr. Ravindra Uppaluri
Discussant Ravindra Uppaluri, MD, PhD, of Washington University School of Medicine, said that the CheckMate 141 trial “continues to highlight the use of PD-L1 status as a stratifier.” The trial results “offer hope for patients with refractory or metastatic HNSCC,” he said. “Obviously better biomarkers are needed, and, ultimately, a composite immune profile may be required.”
*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.