A breakthrough in immunotherapy is changing the outlook for patients with advanced head and neck cancer.
For patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), the treatment landscape has historically been bleak. With few options after platinum-based chemotherapy fails, the prognosis has been poor. However, the CheckMate 141 clinical trial marked a turning point, establishing the immunotherapy drug nivolumab as a new standard of care.
Does prior treatment with the targeted therapy cetuximab affect how well patients respond to subsequent immunotherapy?
Head and neck squamous cell carcinoma is the seventh most common cancer globally, with an estimated 400,000 to 600,000 new cases each year 8 .
The disease often impacts critical functions like breathing, swallowing, and speaking 8 , significantly affecting quality of life.
For cancer that returns or spreads, the five-year survival rate for metastatic disease is tragically low—less than 4% 8 . For decades, treatment options were severely limited for patients whose cancer progressed after platinum-based chemotherapy.
Nivolumab is a PD-1 inhibitor 8 that blocks the PD-1 brake on T-cells. By releasing this brake, nivolumab re-awakens the immune system, allowing T-cells to recognize and attack cancer cells.
Directly attacks cancer cells (and healthy cells in the process), causing significant side effects.
Empowers the body's own immune system to fight the cancer, offering a more targeted approach with fewer side effects.
CheckMate 141 was a global, randomized, phase 3 clinical trial that compared nivolumab to standard single-agent chemotherapy in patients with recurrent or metastatic SCCHN that had progressed during or after platinum-based chemotherapy 2 8 .
Would a patient's prior treatment with cetuximab (a targeted therapy drug that blocks EGFR) 2 affect their response to nivolumab?
361 patients with recurrent or metastatic SCCHN that progressed within 6 months of platinum therapy were enrolled.
Patients were randomly assigned in a 2:1 ratio to receive either nivolumab or investigator's choice therapy.
Randomization was stratified by whether patients had prior cetuximab exposure, ensuring balanced groups.
The results, published in Clinical Cancer Research, were encouraging for both groups of patients 2 .
| Subgroup | Treatment Arm | Median Overall Survival (Months) | Hazard Ratio (HR) |
|---|---|---|---|
| With Prior Cetuximab | Nivolumab | 7.1 | 0.84 |
| Investigator's Choice | 5.1 | - | |
| Without Prior Cetuximab | Nivolumab | 8.2 | 0.52 |
| Investigator's Choice | 4.9 | - |
| Metric | Subgroup | Nivolumab | Investigator's Choice |
|---|---|---|---|
| Objective Response Rate | With Prior Cetuximab | 12.6% | 5.7% |
| Without Prior Cetuximab | 15.7% | 5.8% | |
| Grade 3-4 Treatment-Related Adverse Events | With Prior Cetuximab | 13.6% | 35.7% |
| Without Prior Cetuximab | 15.9% | 33.3% |
A crucial finding was the favorable safety profile of nivolumab. The rate of severe (Grade 3-4) treatment-related adverse events was substantially lower with nivolumab than with chemotherapy in both subgroups 2 . This means that patients not only lived longer, but they also experienced fewer disruptive and dangerous side effects from their treatment.
The following details the primary therapeutic agents used in the CheckMate 141 trial 2 3 .
Monoclonal antibody that blocks the PD-1 receptor on T-cells, "releasing the brakes" on the immune system to attack cancer cells.
Monoclonal antibody that blocks the Epidermal Growth Factor Receptor (EGFR), a protein that promotes cancer cell growth and division.
Interferes with cell division by stabilizing microtubules, thereby stopping cancer cells from multiplying.
Inhibits DNA synthesis and cell reproduction, primarily affecting rapidly dividing cells like cancer cells.
The analysis of CheckMate 141 by prior cetuximab use provided oncologists with the critical evidence needed to confidently use nivolumab in a broad patient population. It demonstrated that prior failure of cetuximab treatment does not preclude a benefit from subsequent immunotherapy with nivolumab 2 .
This finding was a vital piece of the puzzle that cemented nivolumab's role as a standard of care for patients with platinum-refractory recurrent or metastatic SCCHN. It offered a new, effective, and better-tolerated treatment option for a patient group that desperately needed it, truly changing the treatment paradigm for this aggressive cancer.
The success of CheckMate 141 has also paved the way for further research into combination therapies and the use of immunotherapy in earlier lines of treatment for head and neck cancer, continuing to bring hope to patients worldwide.