Powering up non-small cell lung cancer treatment with tumor treating fields

A wearable device harnesses electric fields to enhance treatment outcomes for patients with metastatic non-small cell lung cancer (NSCLC).

The US FDA (MD, USA) has approved Optune Lua®, a wearable electronic device produced by Novocure® (Root, Switzerland), for use in combination with PD-1/PD-L1 immune checkpoint inhibitors or the chemotherapy docetaxel to treat patients with metastatic NSCLC. This approval follows the promising results of a Phase III trial, which showed a significant improvement in median overall survival for patients using Optune Lua alongside these therapies.

Lung cancer is the leading cause of cancer mortality worldwide and NSCLC is by far the largest subtype, accounting for approximately 85% of all lung cancers. In the US, it is estimated that approximately 193,000 patients are diagnosed with NSCLC annually. Treatment is dependent on the stage of the disease and can include a combination of surgery, radiation, chemotherapies like docetaxel and immune checkpoint inhibitors, such as PD-1 and PD-L1.

While there have been significant improvements in initial treatments for NSCLC, this aggressive cancer often progresses despite therapy and effective treatment options in the second line and later stages remain limited.

In this context, Optune Lua offers a novel approach. It is a wearable device that delivers Tumor Treating Fields (TTFields), alternating electric fields specifically designed to target and kill cancer cells. Applied through non-invasive arrays on the skin, these fields exert physical forces on electrically charged structures within cancer cells, disrupting their division and leading to cell death.

In preclinical studies, TTFields have demonstrated multiple effects that hinder cancer growth. They interfere with mitosis by disrupting cell structures like the microtubule network, which impairs cell movement and reduces metastasis. TTFields also stimulate an immune response against tumors and downregulate key genes responsible for DNA replication and repair in cancer cells, further promoting cancer cell death [1]. Through these mechanisms, TTFields present a promising addition to cancer therapy.

The efficacy of Optune Lua was evaluated in the Phase III LUNAR study, a prospective, randomized, open-label trial conducted across multiple centers. The study compared two treatment approaches for patients with metastatic NSCLC whose disease worsened during or after platinum-based chemotherapy. In the experimental group, patients received Optune Lua along with either PD-1/PD-L1 inhibitors or docetaxel, while the control group received only PD-1/PD-L1 inhibitors or docetaxel.

The trial results demonstrated that Optune Lua, when used with PD-1/PD-L1 inhibitors or docetaxel, significantly extended median overall survival (OS) compared to using these therapies alone. Specifically, patients using Optune Lua and a PD-1/PD-L1 inhibitor showed a median OS of 19 months, an increase of over 8 months compared to the inhibitor alone. Patients using Optune Lua with docetaxel had a median OS of 11.1 months versus 8.9 months with docetaxel alone, which showed a positive trend but was not statistically significant.

Side effects linked to the device occurred in 63.1% of patients, primarily skin issues where the transducer arrays were applied. Most of these skin reactions were mild to moderate, while only a small portion developed more severe skin reactions that required a temporary pause in treatment. Importantly, no severe adverse effects were associated with Optune Lua and no device-related side effects were fatal.

Based on these positive results, the FDA approved the use of Optune Lua alongside PD-1/PD-L1 inhibitors or docetaxel for treating adult patients with metastatic NSCLC who have experienced disease progression following or after platinum-based chemotherapy.

With this FDA approval, Optune Lua represents a significant advancement in the treatment landscape for NSCLC, offering patients a non-invasive, portable option that enhances the effectiveness of current therapies.