Lenvatinib Plus Pembrolizumab Shows Promise in HNSCC Trial

Adding lenvatinib to the immunotherapy pembrolizumab appears to extend progression-free survival (PFS) in some patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to recently published trial data. Although, the combination has not yet demonstrated a statistically significant improvement in overall survival (OS), leading to the discontinuation of a key clinical trial investigating its use. This development highlights the complexities of treating advanced HNSCC and the ongoing require for more effective therapies.

Understanding Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a cancer that begins in the squamous cells, which line the mouth, throat, larynx (voice box), and other parts of the head and neck. It’s often linked to tobacco and alcohol use, as well as the increasing role of human papillomavirus (HPV) infection. Recurrent or metastatic HNSCC means the cancer has returned after initial treatment or has spread to distant parts of the body, making it significantly more challenging to treat. The prognosis for patients with advanced HNSCC remains poor, underscoring the urgency to find novel treatment options.

Lenvatinib and Pembrolizumab: How They Function

Lenvatinib is a tyrosine kinase inhibitor, a type of targeted therapy. It works by blocking the activity of certain proteins that promote the growth of blood vessels, thereby cutting off the blood supply to the tumor. Pembrolizumab, is an immunotherapy drug. It’s a type of checkpoint inhibitor that helps the body’s own immune system recognize and attack cancer cells. Checkpoint inhibitors essentially release the brakes on the immune system, allowing it to more effectively fight cancer. Combining these two approaches – targeting the tumor’s blood supply and boosting the immune response – was the rationale behind the LEAP-010 trial.

LEAP-010 Trial: Initial Findings and Discontinuation

The LEAP-010 trial randomly assigned patients with PD-L1 CPS ≥ 1 HNSCC to receive either lenvatinib plus pembrolizumab or placebo plus pembrolizumab. PD-L1 CPS (Combined Positive Score) is a measure of how much of the cancer cells express the PD-L1 protein, which pembrolizumab targets. A higher CPS score generally suggests the cancer may be more responsive to immunotherapy. Whereas the combination showed promise in extending PFS, a key measure of how long patients live without their cancer growing or spreading, the trial was stopped after a preliminary analysis indicated it was unlikely to demonstrate a statistically significant improvement in overall survival. The ASCO Post reported on this outcome.

This outcome is not entirely unexpected. Many cancer treatments show an initial benefit in PFS but ultimately fail to translate into a meaningful improvement in OS. PFS can be influenced by factors other than the drug’s direct effect on survival, such as subsequent therapies patients receive. OS, however, is considered the gold standard endpoint in cancer trials, as it directly measures how long patients live.

Mixed Results and Ongoing Research

The combination of pembrolizumab and lenvatinib has shown mixed results in HNSCC. CancerNetwork highlights the nuances of these findings. While the LEAP-010 trial was discontinued for OS, other studies are exploring the potential of this combination in different settings and with different patient populations. For example, researchers are investigating whether the combination might be more effective in patients with specific genetic mutations or in those who have not received prior treatment.

Limitations of Current Research

It’s important to acknowledge the limitations of the current research. The LEAP-010 trial, like all clinical trials, had specific inclusion and exclusion criteria, meaning the results may not be generalizable to all patients with HNSCC. The trial’s design and statistical analysis can influence the results. The initial projection of OS, which led to the trial’s discontinuation, is based on an interim analysis and may change as more data becomes available. OncLive provides further details on the trial’s discontinuation.

What This Means for Patients

The discontinuation of the LEAP-010 trial does not imply that lenvatinib and pembrolizumab have no role in treating HNSCC. The combination may still be considered in certain clinical situations, particularly for patients who have exhausted other treatment options. However, patients should discuss the potential benefits and risks of this treatment with their oncologist to make an informed decision. It’s crucial to understand that treatment decisions should be individualized based on the patient’s specific circumstances, including the stage of their cancer, their overall health, and their preferences.

The Future of HNSCC Treatment

Research into new treatments for HNSCC is ongoing. Scientists are exploring a variety of approaches, including novel immunotherapies, targeted therapies, and combinations of different treatments. The goal is to develop therapies that are more effective, less toxic, and better tailored to the individual patient. Clinical trials are essential for evaluating these new treatments and determining their potential benefit. Patients interested in participating in a clinical trial should discuss this option with their oncologist.

Next Steps: Ongoing research will focus on identifying biomarkers that can predict which patients are most likely to benefit from lenvatinib and pembrolizumab, and exploring alternative combinations of therapies. Further analysis of the LEAP-010 trial data may too provide valuable insights into the potential role of this combination in specific subgroups of patients.